JS PD KB

KB Build Log

67 min read

KB Build Log

2026-05-01

Started the Obsidian-compatible Markdown wiki under data/processed/kb/.

Pilot scope:

batchsource photosfocus
GBA-PD pilot 120240722_181748 to 20240722_181809GBA-PD summary, biomarker matrix, eliglustat, ambroxol, venglustat, PR001

Initial pages:

Open work:

  • Expand PR001 clinical-trial coverage from 20240722_181813 and following pages.
  • Add entity pages for GBA1, GCase, GlcCer, and GlcSph.
  • Decide whether contradiction tracking belongs in a single page or in per-topic sections.

2026-05-01 (later)

Expanded the wiki from the GBA-PD pilot to a whole-corpus discovery layer.

Added:

  • README.md - build note describing what the KB is and the rules it follows.
  • _sidebar.md - hierarchical navigation (sections, maps, topics, entities).
  • sections/ - 18 aggregator pages, one per nav_path cluster, listing every source assigned to that cluster grouped by nav-path root: gba-pd-asyn (198), parkin (46), inflammation (42), biomarkers-outcomes (27), mitochondria (19), molecular-biology (18), pet-imaging (16), operations (14), pk-gt-pharmacology (11), clinical-pd (9), samples-collaborations (9), genetics-pathway (9), msa (9), other-mechanisms (7), lysosome-autophagy (5), lrrk2 (4), cgas-cgamp (2), microglia-imaging (2). Total: 447.
  • maps/source-catalog.md - flat catalog of all 447 source notes in capture-time order, each row linking to its KB source note, the canonical by-photo Markdown, and the section it was assigned to.

Updated:

  • index.md - now exposes the section catalogue and maps explicitly, with source counts and links. Eliglustat link added (was missing).
  • maps/document-outline.md - expanded from pilot-only to a whole-corpus top-level outline with one row per section and a separate pilot block for the GBA-PD synthesis pages.

Section assignment is heuristic: each source went into one primary cluster based on its nav_path root and a small keyword set. The full nav_path remains in maps/nav-path-index.md and in each per-photo source note for disambiguation. No by-photo Markdown body was modified in this batch; no new image assets added; raw photos remain gitignored.

2026-05-01 (P1 usability fixes)

QA-driven fixes; no narrative synthesis added.

  • topics/by-nav/parkin.md slug collision: merged the Parkin and Parkin, (typo) nav-root variants into a single by-nav index. Row count is 31 on a first-nav_path basis (Parkin 27 + Parkin, 4). Original nav-root spelling is preserved per row in a new nav root column; nav_root_variants recorded in frontmatter. Sources whose first nav root is PARKN GT (Takeshi Hioki, PFR-4249-100) remain in their own by-nav index.
  • All 447 sources/<stem>.md notes now carry an assigned section: section: and section_title: in frontmatter, a Section row in the Source Metadata table, and a Section: link line (pointing to the matching sections/<slug>.md) in the Wiki Coverage block. Mapping mirrors sections/*.md and maps/source-catalog.md exactly.
  • New topics/alpha-synuclein.md alias entry point (type: topic_alias, status: alias). It is not a synthesis page — it only routes a reader to where α-synuclein / aSyn / SNCA evidence already lives (sections/gba-pd-asyn Supplement군, MSA section, PR001/ambroxol/venglustat entities, related by-nav indexes). index.md and _sidebar.md link to it under a new Topic Aliases section.
  • Canonical by-photo Markdown under data/processed/markdown/by-photo/ was not modified. No raw photos staged; no new figure assets added.

2026-05-02

Parkin topic synthesis added on top of the discovery layer.

Added:

  • topics/parkin.md - synthesis page covering all 46 sources in sections/parkin, organised by axis (Parkin protein / gene / KO; Parkin PD prevalence, variants, phenotype, imaging; mitophagy and pS65-Ub; PARKN GT program; PINK-1; clinical cohorts and sample-size; preclinical-support MC1 PET radioligand work). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 186 uncertain spans, 32 embedded images across 46 sources, retained as review surface area.
  • entities/programs/parkn-gt.md - PARKN GT (PFR-4249-100) program entity covering 19 sources whose nav_path is rooted in or sits under PARKN GT (Takeshi Hioki, PFR-4249-100) (plus the trailing-tail Parkin, > TM > Assays > ... > PINK-1 page). Uses the PR001 entity page as a structural reference. Includes 20240722_182103 for program completeness even though it is filed under sections/gba-pd-asyn, because its first nav root is PARKN GT (Takeshi Hioki, PFR-4249-100).

Updated:

  • index.md - linked topics/parkin under Topic Pages and entities/programs/parkn-gt under Entities.
  • _sidebar.md - same two links added under Topic Pages and Entities.

No data/processed/markdown/by-photo/ body content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking by-photo Markdown when source-note headings were not enough to ground a synthesis claim. Domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets.

2026-05-02 (later)

Inflammation topic synthesis added on top of the discovery layer.

Added:

  • topics/inflammation.md - synthesis page covering all 42 sources in sections/inflammation, organised by axis (NLRP3 / Inflammasome / Pyroptosis biology; CAPS and inflammation-related disease models; NLRP3 inhibitor (Marianthi) program distribution; Imaging neuroinflammation and TSPO; Biomarker / cytokine / omics workstreams; Competitor / In Vivo strategy / KOL Havrda + Katy; Complement / C5aR1; Stratification, postmortem, and adjacent strands). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 172 uncertain spans, 0 body-embedded figure assets across 42 sources, retained as review surface area. The zero-figure-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded.
  • entities/programs/nlrp3-inhibitor.md - NLRP3 Inhibitor (Marianthi) (PFR-4231-100) program entity covering 11 sources whose nav_path references the program nav root (in any of the three variant spellings NLRP3 inhibitor (Marianthi) (P...), NLRP3 inhibitor (Marianthi), NLRP3 inhibitor (Marianthi) (PFR-4231-100)). Uses the PARKN GT entity page as a structural reference. Includes 20240722_183153 for program completeness even though the program nav root sits at the last element of its nav_path (kickoff transition page); excludes the Havrda KOL pages (20240722_183225, 20240722_183228) and Katy in-vivo pages (20240722_183234, 20240722_183238, 20240722_183241) that lack the program nav root, deferring them to the topic page’s Competitor / In Vivo Strategy / KOL axis. Totals: 46 uncertain spans, 0 embedded images.

Updated:

  • index.md - linked topics/inflammation under Topic Pages and entities/programs/nlrp3-inhibitor under Entities.
  • _sidebar.md - same two links added under Topic Pages and Entities.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking by-photo Markdown for the 11 NLRP3 inhibitor program pages and the section-page metadata; domain- knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-02 (Mitochondria topic)

Mitochondria topic synthesis added on top of the discovery layer.

Added:

  • topics/mitochondria.md - synthesis page covering all 19 sources in sections/mitochondria, organised by axis (Foundational biology / respiration / structure / Complex I / MAM; Mitochondrial DNA / genes / methylation / turnover / dynamics / regulators; Assessment of mitochondria summary matrix and assay-literature panels; 31P MRS imaging principle / human comparison table / Christen Klein UDCA trials; MC1 PET / [18F]BCPP-EF tracer mechanism / MIND-MAPS / MPTP- monkey / Preclinical-support [3H]BCPP-EF assay log; Mitophagy biology and in-vivo measurement candidates / Padmanabhan biomarker pipeline; TRAP1 protein / MOA / Amathus PAM in vitro pharmacology; MEG / Maiko Tanaka / Metabolomics / MIBG adjacent strand). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 85 uncertain spans, 0 body-embedded figure assets across 19 sources, retained as review surface area. The zero-figure-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded. No new entity page was created; MC1 PET / 31P MRS / TRAP1 (Amathus PAM) are treated as axes within the topic and as related candidates rather than program entities.

Updated:

  • index.md - linked topics/mitochondria under Topic Pages.
  • _sidebar.md - same link added under Topic Pages.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking by-photo Markdown for the 19 mitochondria pages; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-02 (Biomarkers and Outcomes topic)

Biomarkers and Clinical Outcome Measures topic synthesis added on top of the discovery layer.

Added:

  • topics/biomarkers-outcomes.md - synthesis page covering all 27 sources in sections/biomarkers-outcomes, organised by axis (Biomarker development framework / taxonomy / analytical (technical) validation / BMx Milestone Matrix / BAF-BAQ-BCS Validation Milestones / Sin 2015 pipeline / Fluid Biomarker Working Group / Keytruda PD-L1 / MSI-H / dMMR worked example; Clinical scales / cohorts / sample size — Original UPDRS / MDS-UPDRS / Holden 2018 PPMI / Simuni 2018 #198 Table 2 / MoCA / DaTscan vs [18F]AV-133 effect size / sample-size estimations / GLP-1 agonist sample-size anchor; NFL across PD / MSA cohorts — Nocker 2012 DAT, Poewe 2015 DTI, Wild 2009 atrophy, Chelban 2022 #310 MSA, Mollenhauer DeNoPa, MOA of NPC arimoclomol panel; RBD prodromal / stratification axis — GBA → RBD penetrance, RBD → PD/MSA/PDD-DLB conversion, GBA pathway in RBD figure, PSYCHIATRIC OUTCOMES IN PD, Unmet Needs slide, NCNP CSF / Kamiguchi RBD translational thread, LED reference; Retinal imaging / Rob Rubens — Amydis AMDXP-2011P, Veys 2019 / Bodis-Wollner 2014 / Ortuño-Lizarán 2018, Karayel 2021 2257w urine-CSF overlap, Higginbotham 2020 Figure S5 module composite, Yan biomarker planning grid; Synaptic biomarkers / SV2A / Surrogate endpoint / UPS — Wilson 2020 #902 SV2A imaging, neuronal pentraxins, TMEM175 endo-lysosomal current, Succinate / Warburg, Fleming 2012 #2652 Levels-of-evidence taxonomy, UPS schematic / Parkin TR-FRET / ubiquitin detection methods; Adjacent biomarker-planning pages filed under SCOPA-AUT / SILK / biomarkers / Synaptic change in PD first-nav_path heads but whose visible bodies cover SharePoint URL reference table + Sig-1R Cell Mol Neurobiol 2020 schematic, DNA QC / Mutations / SNP Database, Skin Biopsy / ESS / Prevalence / Species difference, and HGVS variant nomenclature / FATHMM / Genotyping). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 111 uncertain spans, 0 body-embedded figure assets across 27 sources, retained as review surface area. The zero-figure-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded. No new entity page was created; the Keytruda / NodThera / Anavex / Amydis / Neuraly / Inflazome competitor and program references are treated as in-axis evidence within the topic rather than program entities. The pre-existing topics/biomarkers.md (GBA-PD pilot range) is left unmodified; its source coverage is disjoint from the 27 sources covered here, and the new page links to it as a sibling pilot synthesis rather than overwriting or merging it.

Updated:

  • index.md - linked topics/biomarkers-outcomes under Topic Pages alongside the (now annotated) GBA-PD pilot topics/biomarkers.
  • _sidebar.md - same link added under Topic Pages alongside the annotated pilot link.
  • topics/biomarkers.md - non-destructive 2-line block-quote added under the H1 to clarify that the page is the GBA-PD pilot synthesis (source set 20240722_181748 to 20240722_181809 under sections/gba-pd-asyn) and that the disjoint whole-section synthesis lives on topics/biomarkers-outcomes. Pilot body (Seed Biomarker Set, Pilot Evidence Notes, Open Structuring Questions) was not modified.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new entity pages; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking by-photo Markdown for the 27 biomarkers-outcomes pages; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-02 (PET / Imaging topic)

PET, Imaging, and Tracer Development topic synthesis added on top of the discovery layer.

Added:

  • topics/pet-imaging.md - synthesis page covering all 18 sources in sections/pet-imaging (16) and sections/microglia-imaging (2), organised by axis (Tracer parameters and outcome-parameters reference framework — Bmax / Kd / Bmax/Kd binding potential / VT / SUV / BPND / R1 / k2 / TRV / COV / ICC / dosimetry / specific activity, anchored on Patel-Gibson 2008, Friden 2014, Honer 2014, McCluskey 2020, Hostetler 2016, Kazami 2019; PET Steering Committee, Workflow, and Lead Optimization — PETSC slide bundle, Discovery Process to FIH Study, Selectivity / cold-tracer LC-MS triage, Preclinical and Clinical study comparison; Regulatory Development Path PET ligand — Mosessian 2014 eIND vs Traditional IND requirements, microdosing study definition, glossary, Timeline-Process Gantt; NLRP3 PET tracer chemistry and in-vivo workstream — [3H]TR-126, TR06647850, TR06683014/15, TR06616126, TR06692993, TR06693098, MCC950 — captured here because the pages’ first nav_path entry is PE / PET / NHP rather than the inflammation cluster; VMAT-2 PET / [18F]AV-133 — Schwarz 2019 NS imaging strategy and Cristian Salina 2022 sample-size analysis with the operator-flagged 45/450 typo preserved verbatim; 7T MRI sequence taxonomy / Hyperintensity / DBM / 7T-PD literature; Microglial Imaging — TSPO rs6971 polymorphism (Mizrahi 2012, Lee 2022), Takeda subject genotype list, NBB case TSPO-class color-coded inventory, Dartmouth / Havrda / IRB / NHP / PDE planning grid; Adjacent off-axis pages filed by heuristic — Radiochemical glossary, Lysosomotropic vs LAMP1-binder lysosomal-tracer comparison, PSYCHIATRIC OUTCOMES IN PD PPMI slide block). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 66 uncertain spans, 0 body-embedded figure assets across 18 sources, retained as review surface area. The zero-figure-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded. No new entity page was created; the Patel-Gibson / Friden / Honer / McCluskey / Hostetler reference frame, the PETSC workflow slides, and the [18F]MNI-1054 / Bavarostat / EKZ-001 / EKZ-317 example tracers are treated as in-axis evidence within the topic rather than program entities. Imaging modalities already covered by the four prior topic syntheses (topics/parkin DATSCAN / 18F-DOPA / FP-CIT / DTI / neuromelanin MRI / [3H]BCPP-EF; topics/mitochondria MC1 PET / [18F]BCPP-EF / 31P MRS / σ1R MAM imaging; topics/inflammation TSPO / DPA714 / FEPPA Imaging neuroinflammation and Microglial Imaging NHP block; topics/biomarkers-outcomes SV2A / σ1R PET / Retinal imaging / DAT / [18F]AV-133) are linked rather than re-stated; each pair of topics shares no source overlap with this page.

Updated:

  • index.md - linked topics/pet-imaging under Topic Pages.
  • _sidebar.md - same link added under Topic Pages.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new entity pages; no new figure assets added; no raw photos staged. Targeted verification was limited to spot- checking by-photo Markdown for the 18 PET / imaging pages and the section-page metadata; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-02 (α-Synuclein topic — full synthesis)

α-Synuclein topic synthesis added on top of the discovery layer, upgrading the prior alias entry to a full Tier 1-centric topic page bounded by maps/alpha-synuclein-source-boundary.md.

Updated:

  • topics/alpha-synuclein.md — type: topic_alias / status: alias replaced with type: topic / status: active; expanded from a 49-line alias-and-routing page into a full synthesis page that narrates only the 39 Tier 1 sources fixed by the boundary map (TAK-341 / MEDI1341 PK/PD model and Clinical studies; SNCA ASO (WAVE) Clinical plan; SNCA BTV (HDO) / PFR-4067-100 Executive summary; aSyn programs Propagation Suppressor / Degrader umbrella; Pipeline of GD & GBA-PD Supplement aSyn chain — Animal models of aSyn (Non-Spreading Models / Spreading Models / Summary of a-syn animal models / MOA of aSyn spreading / Antibodies to aSyn / Astrocytic aSyn / CSF & Blood (a-syn) / Distribution / Expression of aSyn / Function (of normal aSyn) / Mutations SNCA / Postmortem aSyn / Safety for aSyn / KO of α-syn / Seed-Amplification Assay / Sources of aSyn / Skin aSyn / Summary aSyn species / Fragments (Truncation) / Structure of aSyn / Synapse and aSyn / TM for aSyn programs / Turnover of aSyn / ATP13A2 (Park9)); the a-syn POSTMORTEM matrix under Summary > 총정리 GBA protein & activity; the α-Synuclein and Lewy pathology in Parkinson's disease > Supplement Positive vs Negative Lewy-pathology entry; the BioOrchestra aSyn (therapeutic) antibody > Comorbidity page; the Inflammation > NLRP3 > Neuronal > Caspase 1 > aSyn splicing > Catalytic cleft Caspase-1 cross-reference; the `ShareFolder > Mitochondria > Astrocyte > asyn and mitochondria

    Evidence in sPDmitochondria bridge; theMSA > aSyn in MSA CSF aSyn in MSAMSA entry; and the threePipeline of PD aSyn-Antibody / aSyn - Small molecules / aSyn - Vaccinerows. The remaining **145 Tier 2** and **54 Tier 3** sources from the 238 candidates are not re-narrated; they are delegated totopics/parkin(14 T2),topics/inflammation(24 T2),topics/biomarkers-outcomes(15 T2),topics/mitochondria(3 T2),topics/pet-imaging (6 T2), the GBA-PD pilot pages (topics/gba-pd, topics/gba-therapeutics, entities/programs/pr001, entities/compounds/ambroxol, entities/compounds/venglustat, entities/compounds/eliglustat) for the GBA-PD Tier 2 / Tier 3 cluster, sections/msa for the MSA Tier 2 cluster, and the relevant section page for each remaining cluster (operations, samples-collaborations, clinical-pd, lrrk2, lysosome-autophagy, genetics-pathway, other-mechanisms, molecular-biology, pk-gt-pharmacology). The page includes a Source Boundary / Delegation section, a Source Coverage nav-root rollup, axis sections (Foundational Biology; Animal Models; Postmortem and Lewy Pathology; Seed-Amplification Assay; Antibody and Immunotherapy Programs; SNCA-Knockdown Programs; MSA aSyn; Caspase-1 / Inflammation aSyn splicing; ShareFolder Mitochondria asyn-and-mitochondria; ATP13A2 (Park9); GBA-PD ↔ aSyn Link; Parkin / PARKN GT ↔ aSyn Link; Inflammation / Mitochondria / Biomarkers-Outcomes / PET-Imaging Links), a 39- row Source Table (primary provenance ground-truth) with per-page uncertain_span_count/embedded_image_countcopied verbatim from source-notequality_metrics, a compact Tier 2 / Tier 3 source index that points back to the boundary map for per-stem inventory, an Uncertainties Carried Forward block listing the 13 highest-uncertain_span_countTier 1 pages and three cross-page risk notes (PARKN GT decision-matrix scope contradiction; CSF Oligo / total aSyn fold ratio?placeholder; Brain Bank20240722_182722promotion candidate), and a Related Pages block. Totals across the 39 Tier 1 sources: **79 uncertain spans, 12 body-embedded figure assets**, matching the boundary map. Twelve embedded-image counts come from TAK-341 PK/PD model (4) and Clinical studies (2), SNCA BTV / HDO Executive summary (1), SNCA ASO (WAVE) Clinical plan (2), and Pipeline of PDaSyn - Vaccine` (3) — all linked rather than re-embedded per the 2026-04-29 body-purity decision.

Updated:

  • index.md — topics/alpha-synuclein moved out of Topic Aliases and listed under Topic Pages (synthesis) with a Tier 1 caveat link to the boundary map; the now-empty Topic Aliases section heading was removed.
  • _sidebar.md — same move; alias-routing line replaced with a Topic-Pages entry that records Tier 1 (39); Tier 2/3 delegated.
  • maps/alpha-synuclein-source-boundary.md — not modified.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new entity pages; no new figure assets added; no raw photos staged. Targeted verification was limited to spot- checking by-photo Markdown for the 39 Tier 1 pages, source-note nav-path frontmatter, and cross-section delegation owners; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-03 (Therapeutic Programs / Pipeline Overview)

Therapeutic Programs / Pipeline Overview map page added on top of the existing topic / entity layer. The page is a program-routing map and does not re-narrate per-program detail.

Added:

  • topics/therapeutic-programs.md — program map with sections Overview, Source / Page Ownership Rules, Program Matrix (14 rows: PR001, Ambroxol, Venglustat, Eliglustat, PARKN GT (PFR-4249-100), NLRP3 Inhibitor (Marianthi) (PFR-4231-100), TAK-341 / MEDI1341, SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), aSyn programs umbrella, TAK-071, DNL151 (=BIIB12…), DNL201 (=GNE-7…), GAPFREE3 / Preclinical support for the MC1 PET radioligand bench), Existing Entity Pages (6 rows: PR001, PARKN GT, NLRP3 Inhibitor, Ambroxol, Venglustat, Eliglustat), Programs Covered By Topic Pages Only (7 rows: TAK-341, SNCA ASO, SNCA BTV, aSyn programs umbrella, Pipeline-of-PD competitor inventory, Pipeline-of-PD GT row, GAPFREE3 / Preclinical support), Entity Backlog Candidates (9 candidates: TAK-341 → entities/programs/tak-341, SNCA ASO → entities/programs/snca-aso-wave, SNCA BTV → entities/programs/snca-btv-hdo, aSyn programs umbrella → entities/programs/asyn-propagation-suppressor, TAK-071 → entities/programs/tak-071, isofagomine → entities/compounds/isofagomine, GAPFREE3 → entities/programs/gapfree3, DNL151/DNL201 → entities/programs/dnl151, AAV2-GAD / MeiraGTx → entities/programs/aav2-gad), Cross-topic Dependencies, Compact Provenance Table (14 rows: one source-coverage anchor per program row), Uncertainties / Boundary Notes (PARKN GT decision-matrix scope contradiction; NLRP3 program-source vs nav-root scoping; PARKN GT trailing-comma / GBA-PD-section overlap; aSyn Tier 2 / Tier 3 delegation; single-source backlog risk; Pipeline-of-PD competitor scope; body-purity figure-embed boundary), and Related Pages.

Updated:

  • index.md — linked topics/therapeutic-programs under Topic Pages with a “program map; routes to existing topic / entity pages” caveat.
  • _sidebar.md — same link added under Topic Pages with the same caveat.

This pass introduced no new entity pages. Programs missing an entity page (TAK-341, TAK-071, SNCA ASO, SNCA BTV, aSyn programs umbrella, isofagomine, GAPFREE3, DNL151 / DNL201, AAV2-GAD / MeiraGTx) are listed only as Entity Backlog Candidates with suggested slugs.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no other topic / entity page was modified; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking source-note frontmatter for the 14 anchor stems used in the Program Matrix and the Compact Provenance Table; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web / literature search was not used.

2026-05-03 (later, navigation QA)

Final QA / navigation cleanup pass. No new topic / entity / source page created; no data/processed/markdown/by-photo/ body, source-note, section, or by-nav content changed; no new figure assets added; no raw photos staged.

Findings:

  • maps/alpha-synuclein-source-boundary.md was reachable only through the topics/alpha-synuclein Tier 1 caveat. It is now also surfaced under the Maps section in index.md and _sidebar.md.
  • README.md Topics row still described the corpus as having only the GBA-PD pilot synthesis pages (gba-pd, gba-therapeutics, biomarkers); the row now lists all 10 topic pages including the whole-section / cross-section / bounded / program-routing topics.
  • README.md Entities row still described only the four pilot entities; the row now lists all 6 entity pages (3 compounds, 3 programs).
  • README.md Maps row mentioned only the four whole-corpus indexes; the row now also acknowledges alpha-synuclein-source-boundary as a topic-specific planning map.
  • README.md References row now annotates docs/decisions/2026-05-01-audit-status.md as the source of the Uncertain Spans retention policy that KB pages preserve as review targets.
  • maps/document-outline.md GBA-PD Pilot block claimed those were the “only KB pages that combine narrative synthesis with source links”. A new “Topic Synthesis Pages” block is added above the pilot block to enumerate the whole-section / cross-section / bounded / program-routing topics; the pilot block is retained verbatim and the obsolete claim removed.

Validation:

  • 0 broken [[wikilinks]] and 0 broken Markdown links across all 647 KB Markdown files (resolution: relative-to-source first, then vault-root fallback; backtick-wrapped link examples ignored).
  • 18 section pages declared source_count matches the 447 source notes’ section: frontmatter assignments exactly: gba-pd-asyn 198, parkin 46, inflammation 42, biomarkers-outcomes 27, mitochondria 19, molecular-biology 18, pet-imaging 16, operations 14, pk-gt-pharmacology 11, clinical-pd 9, samples-collaborations 9, genetics-pathway 9, msa 9, other-mechanisms 7, lysosome-autophagy 5, lrrk2 4, cgas-cgamp 2, microglia-imaging 2.
  • Topic source-tables match topic frontmatter source_count: parkin 46, inflammation 42, biomarkers-outcomes 27, mitochondria 19, pet-imaging 18 (16 + 2), alpha-synuclein 39 (Tier 1 only).
  • 154 topics/by-nav/ indexes confirmed against the count cited in index.md and _sidebar.md.
  • 447 sources/ notes confirmed against the canonical-corpus count.

Domain-knowledge corrections were not applied; remaining Uncertain Spans are preserved as review targets. External web / literature search was not used.

2026-05-03 (KB wiki v1 status note)

Final v1 release / audit note added under docs/decisions/. No new KB synthesis page created; no data/processed/markdown/by-photo/ body, source-note, section, by-nav, map, topic, or entity page content changed; no new figure assets added; no raw photos staged.

Added:

  • docs/decisions/2026-05-03-kb-wiki-v1-status.md — release / audit note that fixes the v1 scope (discovery layer + 447 source notes + 18 section pages + 6 maps + 10 topic pages + 154 by-nav indexes + 6 entity pages), restates the canonical-source policy (by-photo Markdown is canonical, raw photos are local-only, by-photo / source / section / by-nav corpus is not modified in v1, Uncertain Spans are preserved as review targets), enumerates the completed topic / entity inventory with per-topic uncertain-span and embedded-image totals, documents the provenance traversal (index/sidebar → topic/entity/map → source note → canonical by-photo), captures the v1 verification snapshot (0 broken wikilinks / Markdown links / image embeds across 647 KB Markdown files, 0 by-photo / source / section changes, 0 raw-photo or new .jpg staged), and records remaining P2 / P3 follow-up (frontmatter status normalization, 9 entity-backlog candidates from topics/therapeutic-programs, optional whole-corpus evidence map, topics/by-nav/ regeneration only on corpus change).

Updated:

  • data/processed/kb/README.md — References block now points to the v1 status note alongside the audit-status decision.

Validation:

  • 0 broken [[wikilinks]], 0 broken Markdown links, 0 broken image embeds across all 647 KB Markdown files (resolution: relative-to- source first, then vault-root fallback, then file-stem fallback; fenced code blocks and inline backtick spans excluded; table-cell-escaped wikilinks [[…|…]] resolved correctly).
  • git diff --check clean.
  • data/processed/markdown/by-photo/, data/processed/kb/sources/, data/processed/kb/sections/, data/processed/kb/topics/by-nav/, data/processed/kb/maps/source-catalog.md, data/processed/kb/maps/nav-path-index.md, and data/processed/assets/by-photo/ — no changes.
  • data/raw/photos/<stem>.jpg and any new .jpg — 0 files staged.

Domain-knowledge corrections were not applied; remaining Uncertain Spans are preserved as review targets. External web / literature search was not used.

2026-05-03 (frontmatter status normalization)

Metadata-only cleanup pass for the v1 P2 follow-up listed in docs/decisions/2026-05-03-kb-wiki-v1-status.md (Frontmatter status normalization). No new synthesis added; no body narrative, source table, or source link changed; no data/processed/markdown/by-photo/ content, source note, section page, by-nav index, map, asset, or raw photo touched.

Vocabulary applied to completed topic / entity pages:

  • status: active — whole-section / cross-section / bounded synthesis topics that were finalized in v1 (topics/parkin, topics/inflammation, topics/mitochondria, topics/biomarkers-outcomes, topics/pet-imaging, topics/alpha-synuclein, topics/therapeutic-programs) and the completed program entity pages (entities/programs/parkn-gt, entities/programs/nlrp3-inhibitor).
  • status: pilot — pilot-scoped topic / entity pages limited to the GBA-PD pilot range 20240722_181748–20240722_181809 (topics/gba-pd, topics/gba-therapeutics, topics/biomarkers, entities/compounds/eliglustat, entities/compounds/ambroxol, entities/compounds/venglustat, entities/programs/pr001).

Before / after status table (16 files in scope):

filebeforeafter
topics/gba-pd.mdseedpilot
topics/gba-therapeutics.mdseedpilot
topics/biomarkers.mdseedpilot
topics/parkin.mdseedactive
topics/inflammation.mdseedactive
topics/mitochondria.mdseedactive
topics/biomarkers-outcomes.mdseedactive
topics/pet-imaging.mdseedactive
topics/alpha-synuclein.mdactiveactive (unchanged)
topics/therapeutic-programs.mdactiveactive (unchanged)
entities/compounds/ambroxol.mdseedpilot
entities/compounds/venglustat.mdseedpilot
entities/compounds/eliglustat.mdseedpilot
entities/programs/pr001.mdseedpilot
entities/programs/parkn-gt.mdseedactive
entities/programs/nlrp3-inhibitor.mdseedactive

Source-note (sources/<stem>.md) and by-photo status: fields (e.g., codex_full_transcription_draft) are not affected by this pass. Map pages (maps/), section pages (sections/), per-nav indexes (topics/by-nav/), and templates (templates/) are also not affected.

Validation:

  • 14 files updated (status field only); 2 files (topics/alpha-synuclein, topics/therapeutic-programs) already matched the target vocabulary and were left unchanged.
  • git diff --check: clean.
  • data/processed/markdown/by-photo/, data/processed/kb/sources/, data/processed/kb/sections/, data/processed/kb/topics/by-nav/, data/processed/kb/maps/, data/processed/kb/templates/, and data/processed/assets/by-photo/ — no changes.
  • data/raw/photos/<stem>.jpg and any new .jpg — 0 files staged.
  • Wikilink / Markdown link / image-embed checks were not re-run for this pass: changes are confined to the status: scalar inside frontmatter and do not introduce or remove any link target.

2026-05-03 (alpha-synuclein boundary map doc-drift fix)

Doc-drift fix on maps/alpha-synuclein-source-boundary.md. The map predates the 2026-05-02 alias→active synthesis upgrade of topics/alpha-synuclein.md and still framed the topic as an alias and the synthesis as future. Source counts, tier counts, source tables, provenance links, and the Tier 1 / Tier 2 / Tier 3 inclusion-and- delegation purpose are unchanged.

Updated:

  • data/processed/kb/maps/alpha-synuclein-source-boundary.md — frontmatter key related_topic_alias: → related_topic:; intro paragraph, Inputs entry, Authoring Rules header, Tier 2 / Tier 3 descriptions, Programs and Standalone Nav-Roots paragraph, Tier 1 header, Tier 2 header, Tier 3 header, Exclusion / Delegation Rules header, MSA cluster bullet, Synthesis Shape header and lead sentence, Pages with body-embedded figures description, and the Cross-References entry to topics/alpha-synuclein rewritten to reflect that the topic is now an active full synthesis. Stale phrases removed: “Existing alias entry”, “kept as alias; not promoted to synthesis in this pass”, “the future α-synuclein synthesis / page”, “the future synthesis”, “If a full topics/alpha-synuclein.md synthesis is written next”, “Topics / α-Synuclein (alias)“. The MSA-cluster note was reframed from a recommendation to a resolution and now keeps a forward-looking pointer to a hypothetical future topics/msa.md. Programs paragraph now names the existing axis sections (Antibody and Immunotherapy Programs, SNCA-Knockdown Programs) and references topics/therapeutic-programs Entity Backlog Candidates instead of speculating about whether to seed entities/programs/ pages.

Validation:

  • 0 broken [[wikilinks]], 0 broken Markdown links, 0 broken image embeds across all 647 KB Markdown files (resolution: relative-to- source first, then vault-root fallback, then file-stem fallback; fenced code blocks and inline backtick spans excluded). The new wikilinks [[../topics/alpha-synuclein]] and [[../topics/therapeutic-programs]] resolve correctly.
  • git diff --check: clean.
  • data/processed/markdown/by-photo/, data/processed/kb/sources/, data/processed/kb/sections/, data/processed/kb/topics/by-nav/, data/processed/kb/topics/, data/processed/kb/entities/, data/processed/kb/templates/, data/processed/kb/maps/source-catalog.md, data/processed/kb/maps/nav-path-index.md, and data/processed/assets/by-photo/ — no changes.
  • data/raw/photos/<stem>.jpg and any new .jpg — 0 files staged.
  • The map’s frontmatter tier_1_count (39), tier_2_count (145), tier_3_count (54), and candidate_count (238) are unchanged; the Tier 1 (39 rows), Tier 2 (145 rows), and Tier 3 (54 rows) source tables, the Risk and Uncertainty Notes section, and all [note](../sources/<stem>.md) and [md](/markdown/by-photo/<stem>.md) provenance links are unchanged.

2026-05-03 (MSA topic — whole-section synthesis)

MSA topic synthesis added on top of the discovery layer. The MSA section was the cleanest 0→100% coverage gap in the v1 wiki: 9 sources, no prior topic synthesis, and previously delegated as α-synuclein Tier 2 in the boundary map without a local primary owner.

Added:

  • topics/msa.md — synthesis page covering all 9 sources in sections/msa, organised by axis (Diagnosis of MSA — Gilman 2008 three-level criteria; Genetics, In vitro systems, Imaging, and DATscan; UMSARS, MSA-QoL, and ICLEMSA outcome measures; NfL biomarker — cross-sectional and longitudinal CSF and blood; Pathology — Inclusions, cell loss, splice, subtype comparison; Subtype — urinary / orthostatic symptoms and prevalence; Cohort and natural-history studies — NAMSA-SG, EMSA-SG, TALISMAN, P+A+MS, BioMUSE; Pipeline MSA — Disease-Modifying inventory (BIIB101 / ION464, ATH434, ENT-01, Verdiperstat P2 + P3 M-STAR, AAV2-GDNF, Lu AF82422 AMULET, KM-819, IkT-148009, NMBI / emeramide, Mészáros 2020 #1410 disease-modifying-targets table, Key Ongoing Trials Gantt); Pipeline MSA — Symptomatic; RBD as MSA prodrome — screening, mechanism, pathology / imaging; Mucolipidosis (ML) — TM in MSA cross-reference; Boundary / Delegation). Provenance table includes stem, full nav_path, source-note link, canonical by-photo link, and per-page uncertain_span_count / embedded_image_count copied from source-note frontmatter. Totals: 29 uncertain spans, 0 body-embedded figure assets across 9 sources, retained as review surface area. The zero-figure-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages (Lu AF82422 Bayesian- adaptive timeline, ICLEMSA SRM bar chart and Tables 4 / 5, Pipeline MSA Gantt and Figures 1 / 3, brain-anatomy schematic and MLIV disease-progression curve, Bridel forest plot and Hansson / Ashton / Palleis NfL plots) are kept as evidence rather than embedded.

Boundary with topics/alpha-synuclein:

  • 20240722_184156 (MSA > aSyn in MSA > CSF aSyn in MSA) is Tier 1 of the α-synuclein boundary map and is filed under sections/gba-pd-asyn, not sections/msa. The α-synuclein topic continues to own that page; topics/msa.md does not re-narrate the CSF aSyn / brain aSyn / animal-models-of-MSA material there.
  • The 9 sources of sections/msa are α-synuclein Tier 2 candidates delegated to a sibling topic per the boundary map MSA-cluster bullet. topics/msa.md is the primary owner for those 9 sources and the resolution of the boundary map’s “If a future topics/msa.md is added” forward pointer.
  • The α-synuclein topic Tier 2 / Tier 3 section roll-up msa row is updated from owner [[../sections/msa|sections/msa]] (no synthesis), [[by-nav/pipeline-msa|by-nav/pipeline-msa]] to [[msa|topics/msa]], [[../sections/msa|sections/msa]], [[by-nav/pipeline-msa|by-nav/pipeline-msa]]; the prose delegation note in Source Boundary / Delegation is updated from no MSA topic synthesis exists to owned by [[msa|topics/msa]] (MSA whole-section synthesis); and the MSA aSyn axis lead is updated from The MSA cluster has no topic synthesis to a pointer to topics/msa for cohort / diagnosis / outcome-measure / pathology / subtype / disease-modifying material, while the α-synuclein page still owns the Tier 1 MSA > aSyn in MSA > CSF aSyn in MSA page anchored on 20240722_184156. The MSA aSyn in MSA Tier 1 source _184156 remains in sections/gba-pd-asyn and remains owned by topics/alpha-synuclein — there is no Tier 1 source change.
  • The α-synuclein boundary map MSA cluster Exclusion / Delegation bullet is updated from “If a future topics/msa.md is added, the α-synuclein page will link to it” to a resolution that names topics/msa as the primary owner of the 9 MSA Tier 2 sources. Tier counts (Tier 1: 39 / Tier 2: 145 / Tier 3: 54 / candidates: 238) and the per-stem Tier 1 / Tier 2 / Tier 3 source tables are unchanged.

Updated:

  • index.md — linked topics/msa under Topic Pages.
  • _sidebar.md — same link added under Topic Pages.
  • topics/alpha-synuclein.md — three pointer updates to reflect topics/msa ownership of the 9 MSA Tier 2 sources (delegation bullet, MSA aSyn axis lead, Tier 2 / Tier 3 section roll-up msa row). Tier 1 source 20240722_184156 continues to live in the α-synuclein topic; Source Table is unchanged; no source row added or removed.
  • maps/alpha-synuclein-source-boundary.md — MSA-cluster bullet in Exclusion / Delegation Rules updated from forward-pointer to resolution naming topics/msa as primary owner. Tier counts / source tables / cross-reference links unchanged.
  • log.md — this entry.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no new entity pages; no new figure assets added; no raw photos staged. Targeted verification was limited to spot-checking by-photo Markdown for the 9 MSA pages and the section / source-note metadata; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-03 (TAK-341 / MEDI1341 program entity)

First entity promotion from the therapeutic-programs Entity Backlog Candidates listed in docs/decisions/2026-05-03-kb-wiki-v1-status.md (P2 follow-up). No new topic synthesis added; no data/processed/markdown/by-photo/ body, source-note, section page, by-nav index, map, or other topic / entity page body content was modified beyond the navigation and axis- lead pointers required to record the promotion.

Added:

  • entities/programs/tak-341.md — TAK-341 (MEDI1341) passive- immunotherapy α-synuclein antibody program (Takeda / AstraZeneca / MedImmune). The 5-source set covers the two TAK-341 nav-rooted primary pages (20240722_181818 PK/PD model: TAK-341 mechanism and exon-5 epitope at residues 102–130, MEDI1341 effector-function note, monomer / aggregate KD measurements, DELFIA Aggregated Capture ELISA Figure 4, preclinical aSYN-spreading and MSA postmortem evidence, two-compartment PK/PD model Figure 17, predicted plasma profile and target-suppression Figure 18, Key PK/PD Model Parameters Table 6, Planned MEDI1341 Dose Escalations Table 7 visible cohorts 1 / 5; 20240722_181822 Clinical studies: top comparator-program table TAK-341 vs Prasinezumab, MEDI1341 MAD CSF aSyn POM evidence, TAK-341 rat / NHP preclinical free / total CSF aSyn Figure 14, SAD HV study design, αSYN-vs-341 CSF molarity / relative-concentration calculation, MAD PD study design and biomarker plan, MSA Phase 2 study note FPI in 202207 / BM: NFL) plus the three Pipeline-of-PD cross-pipeline competitor-inventory pages explicitly listed in the therapeutic-programs Program Matrix row for TAK-341 (20240722_184324 aSyn-Antibody eight- program comparison + α-syn sequence diagram + Nitrase NITROME; 20240722_184327 PASADENA Part 1 / 2 / 3 + mAbs summary with TAK-341 (MEDI1341/Aslo452ngl-3) row + aSyn-Small molecules row tail; 20240722_184330 aSyn-Vaccine table + AC Immune PD01A / PD03A AFFiRiS + AFF008 study series + CSF Oligo-aSyn / MDS-UPDRS III correlation + MEDI1341 SAD-study PK table opener). _184333 (Pipeline of PD GT) is excluded; the page continues the MEDI1341 SAD-study PK table from _184330 but is delegated to sections/clinical-pd per therapeutic-programs. The α-synuclein Tier 1 MSA aSyn in MSA page (20240722_184156) and the aSyn programs umbrella (20240722_181827) carry passing TAK-341 references but are owned by alpha-synuclein § MSA aSyn and the upcoming entities/programs/asyn-propagation-suppressor backlog candidate; they are linked from Related Pages rather than re-narrated. Totals across the 5 sources: uncertain_span_count totals 23, embedded_image_count totals 9 (4 on _181818 + 2 on _181822 + 0 on _184324 + 0 on _184327 + 3 on _184330). All 9 figures remain at the canonical by-photo level per the 2026-04-29 body-purity decision.

Updated:

  • index.md — added entities/programs/tak-341 under Entities.
  • _sidebar.md — same link added under Entities.
  • topics/therapeutic-programs.md — Program Matrix row for TAK-341 changed from topic-only (Tier 1) / “No entity page; backlog candidate” to entity (active) with owner tak-341; the row in Existing Entity Pages was added; the Programs Covered By Topic Pages Only TAK-341 row was removed; the Entity Backlog Candidates TAK-341 row was removed; the Single-source backlog risk note no longer lists TAK-341 and now adds tak-341 to the precedent set; the Related Pages owner-entities list adds the new entity; the matrix-summary paragraph now mentions entity (active) alongside entity (seed). Frontmatter related_entities adds programs/tak-341. The KB-status taxonomy in the matrix-summary paragraph was widened to include entity (active) rows alongside entity (seed) rows.
  • topics/alpha-synuclein.md — § Antibody and Immunotherapy Programs TAK-341 axis lead now points to tak-341 for the program-level evidence package and Source Table; the prior in-line narrative is preserved unchanged below the new pointer. The § SNCA-Knockdown Programs umbrella note no longer claims “No dedicated entity page currently exists for TAK-341 / MEDI1341”; the same note clarifies that SNCA ASO (WAVE), SNCA BTV (HDO) / PFR-4067-100, and the aSyn programs umbrella remain backlog candidates without entity pages. Frontmatter related_entities adds programs/tak-341; Related Pages Entities list adds the new entity. Tier 1 source coverage and the 39-row Source Table are unchanged.
  • log.md — this entry.

Boundary observations recorded on the entity page Source Scope And Boundary Notes:

  • The PK/PD-model page 20240722_181818 carries Pipeline of GD & GBA-PD > TAK-341 (MEDI1341) > PK/PD model, so the program nav root is the second nav_path element rather than the first; the page does not appear in tak-341-medi1341 (which keys on the first nav_path entry). It is included because the entire body covers TAK-341 / MEDI1341 mechanism, epitope, affinity, and PK/PD model content.
  • 20240722_181822 (TAK-341 (MEDI1341) > Clinical studies) is the only page indexed under tak-341-medi1341.
  • 20240722_184324 / _184327 / _184330 carry first nav_path entries PDE / Pipeline of PD (not TAK-341 (MEDI1341)); they are included as cross-pipeline rows per the therapeutic-programs Program Matrix anchors.
  • 20240722_184333 is not included; the MEDI1341 SAD-study PK table that begins at the bottom of _184330 continues into _184333, but _184333 is Pipeline of PD > GT and is delegated to clinical-pd under the Programs Covered By Topic Pages Only Pipeline of PD GT row. Readers needing the full MEDI1341 SAD PK table should follow the related-photo continuation note on the _184330 source.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no by-nav / map page content changed; no other entity page body content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot- checking by-photo Markdown for the 5 TAK-341 sources, the source- note frontmatter, the by-nav index, and the four cross-pipeline mention pages used to confirm cross-pipeline membership before deciding the entity boundary; domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-03 (SNCA BTV (HDO) (PFR-4067-100) program entity)

Second entity promotion from the therapeutic-programs Entity Backlog Candidates listed in docs/decisions/2026-05-03-kb-wiki-v1-status.md (P2 follow-up). No new topic synthesis added; no data/processed/markdown/by-photo/ body, source-note, section page, by-nav index, map, or other topic / entity page body content was modified beyond the navigation and axis- lead pointers required to record the promotion.

Added:

  • entities/programs/snca-btv-hdo.md — SNCA BTV (HDO) (PFR-4067-100) α-synuclein knockdown program (Takeda; lead Ryouta Maeda). The single-source set covers the only page indexed under the program nav-root (20240722_181831 Executive summary (Ryouta Maeda), nav_path SNCA BTV (HDO) (PFR-4067-100) > Executive summary (Ryouta Maeda)). The page documents the SNCA BTV (HDO) Plan Table phase columns (LGE / PE: IT / PE: BTV / CN / CS / IND, 2018 (?) LGE marker, PE within FY2022 for IT and the deferred BTV PE, Selected 18개 18mer ASO in vitro screen, Pilot in vivo -> Select one or two ASO, 50% KD (m RNA, at low dose to secure safety margin). Animal model TBD, But SNCA BAC TG (human WT aSyn) is unlikely b/c it does not show pathologic aSn, Focal necrosis is important, Maiko wants to clear this in mice, NHP biodistribution before CN); the DMPK MTV ASO-vs-HDO selection rationale (HDO prioritised because of long plasma duration, better biodistribution, and TfR-conjugated HDO out-distributing TfR- conjugated ASO; ASO not excluded; HDO timeline not significantly different from ASO); the Ryouta Maeda program notes (202104 IT rationale and Every 1-3 m dosing; 20200702 / 20200908 PD / disease / TE marker proposal — total a-syn CSF / oligomer a-syn CSF / SNCA mRNA in plasma NDE; 20220713 differentiation against IONIS IT SNCA ASO BIIB101 by potency, the firewall-bound non- disclosure of the Wave-collaboration discontinuation reason, the MAPT HDO IT failure narrative, and the IT-vs-BTV gating rule); the 20230630 differentiation question list anchored on BIIB101 / ION464: Cole 2021; the SharePoint URL preserved verbatim; the Translation table of aSyn readouts (PK / TE / exposure aSyn mRNA / ↓ aSyn protein / neuroprotection / TfR1 PET / ASO NDE mRNA / aSyn spreading NHP / P aSyn / RT-QuIC / Total aSyn CSF / Asyn PET (QST) / Retinal BM / MIBG / DATscan / Vmri for LBD); the HDO PET Needs And Questions block (purpose visualise drug distribution (not TE, TO), caveat it is uncertain how to quantify? How much is enough?, Paul McQuade lead); the four Paul McQuade 20200923 technical questions; and the HDO PET Development Workflow flowchart (20200521, Steps 1–4). Totals across the 1 source: uncertain_span_count totals 10, embedded_image_count totals 1 (HDO PET Development Workflow flowchart at data/processed/assets/by-photo/20240722_181831/figure_hdo_pet_workflow.jpg). The figure remains at the canonical by-photo level per the 2026-04-29 body-purity decision.

Updated:

  • index.md — added entities/programs/snca-btv-hdo under Entities.
  • _sidebar.md — same link added under Entities.
  • topics/therapeutic-programs.md — Program Matrix row for SNCA BTV (HDO) (PFR-4067-100) changed from topic-only (Tier 1) / “No entity page; backlog candidate” to entity (active) with owner snca-btv-hdo; the row in Existing Entity Pages was added (program code PFR-4067-100, lead Ryouta Maeda); the Programs Covered By Topic Pages Only SNCA BTV row was removed; the Entity Backlog Candidates SNCA BTV row was removed; the Single-source backlog risk note no longer lists SNCA BTV and now adds snca-btv-hdo to the precedent set as the closest single-source aSyn-program entity precedent; the Related Pages owner-entities list adds the new entity; the matrix-summary paragraph now mentions SNCA BTV (HDO) (PFR-4067-100) and TAK-341 / MEDI1341 as the most recent active promotions. Frontmatter related_entities adds programs/snca-btv-hdo.
  • topics/alpha-synuclein.md — § Antibody and Immunotherapy Programs SNCA BTV (HDO) (PFR-4067-100) axis lead now opens with a pointer to snca-btv-hdo for the program-level evidence package and Source Table; the prior in-line narrative is preserved unchanged below the new pointer. The § SNCA-Knockdown Programs umbrella note no longer claims that SNCA BTV (HDO) / PFR-4067-100 has no entity page; the same note clarifies that SNCA ASO (WAVE) and the aSyn programs umbrella remain backlog candidates without entity pages. Frontmatter related_entities adds programs/snca-btv-hdo; Related Pages Entities list adds the new entity. Tier 1 source coverage and the 39-row Source Table are unchanged.
  • log.md — this entry.

Boundary observations recorded on the entity page Source Scope And Boundary Notes:

  • The single source page 20240722_181831 carries the program nav root SNCA BTV (HDO) (PFR-4067-100) as its first nav_path entry, so the strict “first nav_path entry == program nav root” rule applies without exception. It is the only page indexed under snca-btv-hdo-pfr-4067-100.
  • The aSyn programs umbrella page (20240722_181827) carries a portfolio-grid row labelled SNCA BTV (Brain Transport Vehicle: ASO/HDO + transferrin receptor (TfR) ligand): Maeda Ryota (SNCA HDO의 후예) along with the SNCA BTV TfR construct / TfR / TTR PaddleOCR-vs-Apple reading ambiguity; that umbrella page is the canonical owner of the aSyn programs umbrella and is delegated to the upcoming entities/programs/asyn-propagation-suppressor backlog candidate. It is referenced via Related Pages on the entity rather than re- narrated.
  • The SNCA ASO (WAVE) source 20240722_181835 is the sibling SNCA- knockdown program entry and is referenced indirectly through the IT ASO/HDO comparison narrative on 20240722_181831. It is referenced via Related Pages rather than re-narrated.
  • The Pipeline-of-PD aSyn - Antibody / aSyn - Small molecules / aSyn - Vaccine cross-pipeline pages do not list SNCA BTV / HDO modality rows and are excluded.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no by-nav / map page content changed; no other entity page body content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot- checking by-photo Markdown for the 1 SNCA BTV / HDO source, the source-note frontmatter, the by-nav index, the alpha-synuclein boundary map row, the aSyn programs umbrella page (used to confirm the boundary note), and the SNCA ASO (WAVE) source (used to confirm the sibling cross-reference); domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-03 (SNCA ASO (WAVE) program entity)

Third entity promotion from the therapeutic-programs Entity Backlog Candidates listed in docs/decisions/2026-05-03-kb-wiki-v1-status.md (P2 follow-up). No new topic synthesis added; no data/processed/markdown/by-photo/ body, source-note, section page, by-nav index, map, or other topic / entity page body content was modified beyond the navigation and axis- lead pointers required to record the promotion.

Added:

  • entities/programs/snca-aso-wave.md — SNCA ASO (WAVE) α-synuclein knockdown program (Takeda–Wave Life Sciences collaboration; deck footer Takeda-Wave Collaboration Confidential / Takeda-Wave MAPT/SNCA JPT / April 29, 2021). The single-source set covers the only page indexed under the program nav-root (20240722_181835 Clinical plan of SNCA ASO, nav_path SNCA ASO (WAVE) > Clinical plan of SNCA ASO). The page documents the SNCA ASO PK/PD Relationship In Transgenic Mice block (Single ICV, 100 ug, A53T SNCA mice → 1.2-1.9x better KD (vs IONIS) and 3.5-7.4x better Exposure (vs Ionis); the four-clone PK/PD table for WV-36397 / WV-37643 / WV-39172 / WV-42827 in cortex and striatum with t1/2 (week), IC50** (ug/g), Imax, and Projected KD at 8 weeks at 100 ug/g rows; footnotes covering NE, *, **, ***, and the projected-KD extrapolation rule); the Clinical Plan Of SNCA ASO (P1b/2 IT, Early PD, 3-4 dose levels, Q monthly → Q3 m dosing, N=2 sentinel → N~4/arm → N~15/arm expansion gated on CSF aSyn at <=6 mo; POM will be informed by CSF aSyn. ePOC will be informed by NfL and DaT or VMAT2 imaging at ~ month 12.); the Proposed Ph1b/2 Study diagram labels (FIH study, Extension study, Q mo dosing, Measure t1/2, Q 3mo dosing, Dosing, CSF aSyn, DaT scan or VMAT2 PET); the PET SNCA ASO biodistribution narrative (Takeda-Imaging-led radiolabel-development effort to map relative brain ASO concentration in striatum vs cerebral cortex, with cardiac-cycle synchronisation and saline-chaser injection-paradigm precedents); and the SNCA ASO Questions block split across Target Population (PD (early vs late) vs MSA?), Target aSyn KD Efficacy (PD priority over MSA, MOUSE & NHP translation, mRNA- vs-protein effect on total, p-asyn, oligomeric with staining not done, NDE), PK/PD (NHP spreading model used as human-dose- estimation gating tool with initial data expected by July 2020; Mouse spreading model ever tested? -> no), and Administration (IT, Frequency (3m, but TAU prefers ICV device, removal is easy)). Totals across the 1 source: uncertain_span_count totals 7 (the four SNCA ASO-portion uncertainties: nav path inference, Imax placement under WV columns, projected-KD footnote marker, and the a(and biomarker calibration?)? a Key go/no-go criteria? shorthand; the remaining three uncertainties on the canonical page belong to the TAK-071 portion and are delegated out per Source Scope And Boundary Notes), embedded_image_count totals 2 (the in-scope SNCA ASO Proposed Ph1b/2 Study design diagram at data/processed/assets/by-photo/20240722_181835/diagram_snca_aso_ph1b2_design.jpg and the out-of-scope TAK-071 crossover diagram at data/processed/assets/by-photo/20240722_181835/diagram_tak071_crossover_design.jpg). Both figures remain at the canonical by-photo level per the 2026-04-29 body-purity decision.

Updated:

  • index.md — added entities/programs/snca-aso-wave under Entities.
  • _sidebar.md — same link added under Entities.
  • topics/therapeutic-programs.md — Program Matrix row for SNCA ASO (WAVE) changed from topic-only (Tier 1) / “No entity page; backlog candidate” to entity (active) with owner snca-aso-wave; the row in Existing Entity Pages was added (no program code; lead —; modality Takeda / Wave Life Sciences); the Programs Covered By Topic Pages Only SNCA ASO row was removed; the Entity Backlog Candidates SNCA ASO (WAVE) row was removed; the Single-source backlog risk note no longer lists SNCA ASO and now adds snca-aso-wave to the precedent set as the closest single-source aSyn-program entity precedent (alongside SNCA BTV (HDO) (PFR-4067-100) and TAK-341 / MEDI1341); the Related Pages owner-entities list adds the new entity; the matrix-summary paragraph now mentions SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), and TAK-341 / MEDI1341 as the most recent active promotions. Frontmatter related_entities adds programs/snca-aso-wave.
  • topics/alpha-synuclein.md — § Antibody and Immunotherapy Programs SNCA ASO (WAVE) axis lead now opens with a pointer to snca-aso-wave for the program-level evidence package and Source Table; the prior in-line narrative is preserved unchanged below the new pointer. The § SNCA-Knockdown Programs umbrella note no longer claims that SNCA ASO (WAVE) has no entity page; the same note now records that only the aSyn programs umbrella remains as a backlog candidate without an entity page. Frontmatter related_entities adds programs/snca-aso-wave; Related Pages Entities list adds the new entity. Tier 1 source coverage and the 39-row Source Table are unchanged.
  • log.md — this entry.

Boundary observations recorded on the entity page Source Scope And Boundary Notes:

  • The single source page 20240722_181835 carries the program nav root SNCA ASO (WAVE) as its first nav_path entry, so the strict “first nav_path entry == program nav root” rule applies without exception at the nav-root level. It is the only page indexed under snca-aso-wave.
  • The same canonical photo also carries unrelated TAK-071 program content (TAK-071 Clinical Plan, TAK-071 Cognition Result Note, TAK-071 Power Table Fragment, plus the body-embedded diagram_tak071_crossover_design.jpg figure asset). That TAK-071 material is recorded as out of scope for this entity and remains owned by therapeutic-programs § Entity Backlog Candidates TAK-071 row and by gba-pd-asyn; the canonical TAK-071 nav-root page is 20240722_181839. Three of the seven Uncertain Spans on 20240722_181835 belong to the TAK-071 portion and are delegated out (TAK-071 row label K-1-02 OC study partial-cut, the Js: Mean & sd 사용시 / Js: LSM 사용시 Korean / English notation, and the highlighted TAK-071 power-table row 0.49 / ? / ? / 36 / 36 / ? / 0.62).
  • The aSyn programs umbrella page (20240722_181827) carries portfolio-grid rows that include the SNCA ASO modality in its SM-vs-mAb-vs-ASO/NAM differentiation tables and is the canonical owner of the aSyn programs umbrella; it is referenced via Related Pages on the entity rather than re-narrated.
  • The SNCA BTV (HDO) (PFR-4067-100) source 20240722_181831 is the sibling SNCA-knockdown program entry, owned by snca-btv-hdo. It references SNCA ASO (WAVE) indirectly through its IT ASO/HDO comparison narrative and the Ryouta Maeda 20220713 differentiation paragraph against IONIS’s BIIB101, but it does not carry SNCA ASO (WAVE) program data tables. It is referenced via Related Pages rather than re-narrated.
  • The Pipeline-of-PD aSyn - Antibody / aSyn - Small molecules / aSyn - Vaccine cross-pipeline pages do not list a SNCA ASO (WAVE) row and are excluded.
  • The IONIS comparator BIIB101 / ION464 (Cole 2021) referenced as the SNCA ASO competitive anchor is recorded on the SNCA BTV (HDO) source page (20240722_181831) rather than on the SNCA ASO (WAVE) source page; per the cross-program rule on therapeutic-programs § Entity Backlog Candidates, IONIS BIIB101 / ION464 is treated as external comparator evidence and is not promoted to a program row on this entity page.

No data/processed/markdown/by-photo/ body content changed; no data/processed/kb/sources/ or data/processed/kb/sections/ content changed; no by-nav / map page content changed; no other entity page body content changed; no new figure assets added; no raw photos staged. Targeted verification was limited to spot- checking by-photo Markdown for the 1 SNCA ASO (WAVE) source, the source-note frontmatter, the by-nav index, the alpha-synuclein boundary map row, the aSyn programs umbrella page (used to confirm the boundary note), and the SNCA BTV (HDO) source (used to confirm the sibling cross-reference); domain-knowledge corrections were not applied. Remaining Uncertain Spans are preserved as review targets. External web/literature search was not used.

2026-05-03 (aSyn Propagation Suppressor / aSyn programs umbrella entity)

Fourth entity promotion from the therapeutic-programs Entity Backlog Candidates (docs/decisions/2026-05-03-kb-wiki-v1-status.md P2 follow-up). With this promotion all four aSyn-cluster program nav-roots in the corpus (TAK-341 (MEDI1341), SNCA ASO (WAVE), SNCA BTV (HDO) (PFR-4067-100), and aSyn programs > aSyn Propagation Suppressor) now have dedicated entity pages.

Added:

  • entities/programs/asyn-propagation-suppressor.md — single-source entity covering the small-molecule SM Propagation Suppressor and aSyn Degrader axes under the aSyn programs nav root (20240722_181827, the only page indexed under asyn-programs). Per-axis evidence (Old Portfolio Entry milestone grid, aSyn Degrader patient selection, aSyn Propagation Suppressor in-vitro models, Expected MOA of HIT molecules pathway diagram, PFF-screen Targets reference {Bieri, 2019 #1778}, SM-vs-αS-mAb-vs-ASO/NAM differentiation comparison) lives in the entity’s Evidence Package and Key Source Interpretations and is not duplicated here. Totals: uncertain_span_count = 7, embedded_image_count = 0 (the four figure-like artifacts on the page are recorded as evidence-only crops per the page’s format_notes and the 2026-04-29 body-purity decision). The entity opens by stating it is not a meta-page over tak-341, snca-aso-wave, or snca-btv-hdo — those sibling entities own their own program data, and the _181827 page’s top-of-page portfolio-grid fragment and SM-vs-mAb-vs-ASO/NAM comparison are treated as in-source evidence for the SMOL track rather than as sibling-program narrative.

Updated:

  • index.md, _sidebar.md — Entities section adds entities/programs/asyn-propagation-suppressor.
  • topics/therapeutic-programs.md — Program Matrix row for aSyn programs umbrella flipped from topic-only (Tier 1) to entity (active) with the new entity as owner; row added to Existing Entity Pages; row removed from Programs Covered By Topic Pages Only and from Entity Backlog Candidates; Single-source backlog risk note no longer lists the umbrella and adds the new entity to the precedent set; matrix-summary paragraph now reads all four aSyn-cluster rows on entity pages; frontmatter related_entities adds programs/asyn-propagation-suppressor.
  • topics/alpha-synuclein.md — § Antibody and Immunotherapy Programs aSyn programs > aSyn Propagation Suppressor axis lead opens with a pointer to the new entity; § SNCA-Knockdown Programs (umbrella) note records that all four aSyn-cluster nav-roots have entity pages. Prior in-line narrative is preserved unchanged. Tier 1 source coverage and the 39-row Source Table are unchanged. Frontmatter related_entities and Related Pages Entities list both add the new entity.
  • maps/alpha-synuclein-source-boundary.md — only the § Programs and Standalone Nav-Roots intro narrative paragraph was updated to record that all four aSyn-cluster program nav-roots now have entity pages, replacing the prior “No entity page covers TAK-341, MEDI1341, SNCA ASO (WAVE), SNCA BTV (HDO), or aSyn Propagation Suppressor” sentence. Tier 1 / Tier 2 / Tier 3 counts, the per-tier source tables, the Synthesis Outline, the Risk and Uncertainty Notes, and all canonical-source rows are unchanged.
  • log.md — this entry.

Boundary observations recorded on the entity (full list lives in the entity page’s Source Scope And Boundary Notes):

  • Strict “first nav_path entry == program nav root” rule applies to 20240722_181827 without exception.
  • TAK-341 sibling pages (_181818, _181822; _181822 is the preceding-photo of _181827), SNCA BTV (HDO) (_181831; the following-photo of _181827), and SNCA ASO (WAVE) (_181835) are owned by their own entity pages and referenced via Related Pages rather than re-narrated.
  • Pipeline-of-PD competitor pages (_184324, _184327, _184330) do not list a SMOL / aSyn Degrader row and remain owned by alpha-synuclein § Antibody and Immunotherapy Programs.
  • TM for aSyn programs Supplement-axis pages (_182606, _182609) are α-synuclein biology supplement pages (structure / synapse / turnover axis), not program-portfolio pages, and remain owned by alpha-synuclein § Foundational Biology.

Verification: 0 broken wikilinks / Markdown links / image embeds across all 652 KB Markdown files. git diff --check clean. No canonical by-photo body, source-note, section-page, source catalog, nav-path index, by-nav index, or other entity-page body content changed; no new figure assets added; no raw photo / new .jpg staged. Targeted verification limited to spot-checking the canonical _181827 page, its source-note frontmatter, the asyn-programs by-nav index, and the three sibling entity pages used to confirm the boundary notes; domain-knowledge corrections were not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (GBA-PD biology topic synthesis)

GBA / GD / GBA-PD biology bounded topic synthesis added on top of the gba-pd-asyn section. The 36-source set is fixed by the source-boundary map drawn for the sub-topic and is bounded against five sibling owners (GBA-PD pilot, α-synuclein Tier 1, GBA / GCase modality cluster, TAK-071 program, PARKN GT cross-filed page, supplement anatomy chain, BioOrchestra biomarker / Brain Bank cluster).

Added:

  • topics/gba-pd-biology.md — bounded synthesis covering the 36 source pages that build Takeda’s integrative GBA / GD / GBA-PD biology block under Pipeline of GD & GBA-PD > Summary / … > GBA / … > GD / … > GBA-PD. Four reading-order axes: Summary / 총정리 GBA protein & activity chain (10 pages, including the PR001A clinical-trial bridge _181813 that closes the GBA-PD pilot, the Page 144 총정리 GBA protein & activity matrix block at _182123–_182146, and the Page 197 Summary > GBA Sidransky-2012-review hand-off _182153); GBA biochemistry (6 pages — structure, BGL activity, catalytic pathway, gangliosides, GlcSph); Gaucher Disease (GD) biology (11 pages — mutation summary, GD1 / GD3 / Types and Neuropathology, Animal models of GD with the nGD outcome measure leaf, Oculomotor measurements, Retina in nGD); and GBA-PD biology (9 pages — Mutation GBA-PD, MOA GBA-PD, Motor vs Cognition, Animal models of GBA-PD, Correction studies, GBA vs UPDRS vs MOCA). Source Boundary / Delegation section records the five sibling owners; Source Coverage records that all 36 sources share the same first nav_path entry (Pipeline of GD & GBA-PD). Provenance Source Table includes per-source stem, nav_path, source-note link, canonical by-photo link, uncertain_span_count, and embedded_image_count. Totals across the 36 sources: uncertain_span_count = 104 (Summary 57, GBA biochem 13, GD 23, GBA-PD 11); embedded_image_count = 2 (both on _181813). Numbers are review surface area, not resolutions. α-synuclein POSTMORTEM page 20240722_182149 interleaves between _182146 and _182153 in the same Summary chain in capture order but is owned by alpha-synuclein § Postmortem and Lewy Pathology and is not added to this topic’s Source Table; it is referenced in Uncertainties Carried Forward as the in-Summary cross-link.

Updated:

  • index.md — Topic Pages list adds gba-pd-biology between GBA Therapeutics and the GBA-PD-pilot Biomarkers entry.
  • _sidebar.md — Topic Pages list adds the same entry under the same position.
  • log.md — this entry.

Boundary observations recorded on the topic page Source Boundary / Delegation:

  • GBA-PD pilot range (20240722_181748–_181809, 6 pages) is owned by gba-pd, gba-therapeutics, biomarkers, and the eliglustat / ambroxol / venglustat compound entities + PR001 program entity. Linked, not re-narrated. The Summary axis includes _181813, which is just outside the 6-page pilot range but carries the PR001A PROPEL / PROVIDE / PROGRESS / PROCEED and GBA-PD Clinical Trial Comparison Table content; PR001 program detail and the miglustat / S-181 / NCGC607 entries are delegated to pr001 and gba-therapeutics respectively.
  • α-synuclein Tier 1 (per alpha-synuclein-source-boundary), in particular the a-syn POSTMORTEM page 20240722_182149 interleaved into the Summary chain between _182146 and _182153 in capture order, is owned by alpha-synuclein § Postmortem and Lewy Pathology.
  • GBA / GCase modality cluster (20240722_182326, _182330, _182333–_182419 — PET Imaging GBA, GBA Activator, GBA GT, RD-DDU, GALC, KD pipeline, etc.) is not synthesised yet; delegated to a future Cluster B synthesis and remains aggregated on gba-pd-asyn.
  • TAK-071 program (20240722_181839) is delegated to the therapeutic-programs Entity Backlog Candidates TAK-071 row.
  • PARKN GT cross-filed page (20240722_182103) is owned by parkn-gt (the PARKN GT entity already includes _182103 for program completeness even though it sits in sections/gba-pd-asyn).
  • Supplement anatomy chain (20240722_182422–_182447) is section-only; it remains aggregated on gba-pd-asyn without a dedicated topic synthesis.
  • BioOrchestra biomarker chain (20240722_182617–_183115) and Brain Bank pages (_184200, _184203) are delegated to a future Cluster C / D synthesis.

alpha-synuclein is not modified in this pass. Cluster A pointer cleanup (e.g. adding a back-pointer from the α-synuclein § Postmortem and Lewy Pathology axis to this topic) can happen later as a small separate pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all 653 KB Markdown files. git diff --check clean. No canonical by-photo body, source-note, section-page, source catalog, nav-path index, by-nav index, or entity-page body content changed; the only mutated files are topics/gba-pd-biology.md (new), index.md, _sidebar.md, and log.md. No new figure assets added; no raw photo / new .jpg staged. Source Table contains exactly the 36 specified stems. Targeted verification limited to source-note frontmatter for the 36 stems and spot-checking a small set of canonical by-photo pages (_181813, _182123, _182153, _182157, _182216, _182233, _182255, _182259, _182303, _182310, _182316) to confirm axis assignment; domain-knowledge corrections were not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (GBA / GCase modality residual Cluster B)

GBA / GCase therapeutic-modality bounded topic synthesis (Cluster B) added on top of gba-pd-asyn. The 16-source set is the modality cluster that gba-pd-biology explicitly delegated as “future Cluster B synthesis”.

Added:

  • topics/gba-gcase-modalities.md — bounded synthesis covering the 16 source pages under Pipeline of GD & GBA-PD > GBA-PD > PET Imaging GBA / … > GBA Activator / … > GBA GT and sub-leaves. Four axes: PET Imaging GBA / modality readout bridge (3), GBA Activator (5), GBA GT (3), Substrate-pathway correction (5). Source Boundary / Delegation bounds against GBA-PD biology block (_181813, _182123–_182146, _182153–_182323), GBA-PD pilot range (_181748–_181809), α-synuclein Tier 1 + aSyn program entities, PARKN GT cross-filed page (_182103), supplement anatomy chain (_182422–_182447), and the BioOrchestra / Brain Bank chains delegated to future Cluster C / D. Totals across the 16 sources: uncertain_span_count = 14, embedded_image_count = 0. Per-source detail lives on the topic page; this log entry does not duplicate the Source Table.

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/gba-gcase-modalities between GBA-PD Biology and the GBA-PD-pilot Biomarkers entry.
  • log.md — this entry.

No new entity pages were created in this pass; program-style rows visible on the 16 source pages remain therapeutic-programs Entity Backlog Candidates rather than being promoted here. gba-pd-biology is not modified in this pass; the back-pointer from its Source Boundary / Delegation row for the “future Cluster B synthesis” can be cleaned up in a separate small pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all 654 KB Markdown files. git diff --check clean. No canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, or entity-page content changed; the only mutated files are topics/gba-gcase-modalities.md (new), index.md, _sidebar.md, and log.md. No new figure assets added; no raw photo / new .jpg staged. Source Table contains exactly the 16 specified stems. Domain-knowledge corrections were not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (Brain Bank residual Cluster D)

Brain Bank / Biobank / Postmortem sample-landscape bounded topic synthesis (Cluster D) added on top of gba-pd-asyn. The 12-source set covers the brain-bank / biobank / postmortem sample landscape that gba-pd-biology and gba-gcase-modalities both explicitly delegated as “future Cluster D synthesis”, excluding the BioOrchestra biomarker catalog (delegated to a future Cluster C).

Added:

  • topics/brain-banks-postmortem.md — bounded synthesis covering 10 source pages on the Page 407 / 423 / 440 capture-time band under Pipeline of GD & GBA-PD > Supplement > … > Biobank > MJF > Netherlands Brain Bank > Imperial College Brain Bank > Other Biobanks > Biobanks in Japan > BIOMARKER (20240722_182617, _182620, _182624, _182627, _182630, _182634, _182637, _182641, _182644, _182704) plus the two standalone Brain Bank nav-root pages on Page 925 (20240722_184200, 20240722_184203). Three axes: Biobank / brain-bank landscape (7) — MJF (PPMI / BioFiND / LCC / S4 / Nilo-PD), NBB tissue request flow, ICBB ~400 genotyped PD cases, Other Biobanks (UK BBN / NIH NeuroBiBank / NCRAD / vendors / fibroblast lines / Munich / Banner Brain), Biobanks in Japan (J-PPMI / Niigata / TMM / Tsukuba / Kyoto-U Nagahama); BIOMARKER tracker bridge (3) — Biobanks-in-Japan tail, BM-Tracking KPI matrix, lysosomal-marker / aSyn / GlcSph / pSer65-Ub assay rows tied to MJ / NBB / J-PPMI / NDE samples, MITOKININ NBB CSF and BoMM 240 NBB samples; Standalone Brain Bank — MSA postmortem / cohort axis (2) — Oligomeric / RT-QuIC / RBC / Skin aSyn in MSA, Autonomic Failure, HORC-MSA cohort and MSAR / BIOMUSE row.

    Source Boundary / Delegation bounds against the BioOrchestra biomarker chain (_182708–_183115, future Cluster C), α-synuclein Tier 1 + aSyn program entities, GBA-PD biology block, GBA / GCase modalities, the GBA-PD pilot range, the supplement anatomy chain, MSA section pages, the samples-collaborations operations / logistics-only pages (P2P / NDU / Neurogenomics Partnership / Pittsburgh / SECONDMENT / Liquid Nitrogen — deferred as out of scope here), and the PARKN GT cross-filed page.

    Totals across the 12 sources: uncertain_span_count = 10 (concentrated on the two standalone Brain-Bank pages, _184200 6 + _184203 4; the 10 supplement-chain pages each record 0); embedded_image_count = 0. Per-source detail lives on the topic page; this log entry does not duplicate the Source Table. The Brain Bank standalone pages live in sections/gba-pd-asyn per source-catalog assignment, so this is bounded inside gba-pd-asyn rather than cross-section. The alpha-synuclein boundary map already delegates the entire _182617 → _183115 range (plus _184200, _184203) under its “Brain Bank / BioOrchestra biomarker-catalog cluster” rule; five of the twelve stems (_182617, _182630, _182644, _184200, _184203) are also individually flagged Tier 2 “Brain bank / postmortem aSyn-adjacent” in that map’s candidate table. All twelve remain delegated from alpha-synuclein § Tier 1 to this Cluster D topic.

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/brain-banks-postmortem between GBA / GCase Therapeutic Modalities and the GBA-PD-pilot Biomarkers entry.
  • log.md — this entry.

No new entity pages were created in this pass; biobank, brain-bank, vendor, and cohort entries listed on the source pages remain catalog rows on the canonical by-photo files. The brain-bank generated index (2 stems) is not modified; gba-pd-biology and gba-gcase-modalities are not modified in this pass — back-pointer cleanup from their “future Cluster D synthesis” rows can be done in a separate small pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all 655 KB Markdown files. git diff --check clean. No canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, or entity-page content changed; the only mutated files are topics/brain-banks-postmortem.md (new), index.md, _sidebar.md, and log.md. No new figure assets added; no raw photo / new .jpg staged. Source Table contains exactly the 12 specified stems. Domain-knowledge corrections were not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (BioOrchestra biomarker catalog residual Cluster C)

New catalog/index page bioorchestra-biomarker-catalog (status: active, source_count: 74, section: gba-pd-asyn) covering the BioOrchestra biomarker catalog band — the residual cluster that brain-banks-postmortem, gba-pd-biology, gba-gcase-modalities, and alpha-synuclein boundary map explicitly delegated to “future Cluster C”.

Scope: capture-time range 20240722_182708–20240722_183115 under the shared nav_path prefix Pipeline of GD & GBA-PD > Supplement > Other Biobanks > Biobanks in Japan > BIOMARKER > BioOrchestra > … (75 chain rows; _183050 excluded as α-synuclein Tier 1, owned by alpha-synuclein). Page shape is catalog/index, not narrative synthesis: 11 buckets C0–C11 from the QA plan, fixed-schema 74-row Catalog Source Table, 39-row α-Synuclein- Adjacent Rows table (Tier 2 boundary tag only), per-stem Uncertainties Carried Forward. All 74 source notes verified for nav_path / source_headings / quality_metrics; embedded_image_count = 0 for every stem; aggregate uncertain_span_count = 144.

Sibling delegation rewrites (active page links replacing the “future Cluster C” placeholder wording; no Source Tables / tier counts / primary source sets touched): topics/brain-banks-postmortem.md (5 spots — intro paragraph, Source Boundary table row, Source Boundary trailing sentence, BIOMARKER Tracker Bridge tail, Uncertainties Carried Forward BIOMARKER → BioOrchestra row); topics/gba-pd-biology.md and topics/gba-gcase-modalities.md § Source Boundary tables (combined “BioOrchestra biomarker chain · Brain Bank” row split into Cluster C and Cluster D rows); topics/alpha-synuclein.md § Source Boundary / Delegation Brain Bank / BioOrchestra cluster bullet (active links to Cluster C and Cluster D); maps/alpha-synuclein-source-boundary.md § Borderline Calls and § Risk and Uncertainty Notes (active-ownership lines appended); index.md and _sidebar.md (new topic entry).

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/bioorchestra-biomarker-catalog.md (new), topics/brain-banks-postmortem.md, topics/gba-pd-biology.md, topics/gba-gcase-modalities.md, topics/alpha-synuclein.md, maps/alpha-synuclein-source-boundary.md, index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 74 specified stems; _183050 is excluded and delegated; 39 α-synuclein Tier 2 stems tagged but not narrated. Domain-knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (molecular-biology whole-section topic synthesis)

Whole-section topic synthesis added on top of molecular-biology. The 18-source set covers the late-document [MOLECULAR BIOLOGY] / [Protein] / Proteomics / [Glossary] methodology chapters that the rest of the JS PD pipeline cites for vocabulary, assay families, and HGVS nomenclature.

Added:

  • topics/molecular-biology.md — whole-section synthesis covering all 18 source pages assigned to sections/molecular-biology (capture-time range 20240722_184417–20240722_184901). Six axes: Central Dogma / DNA-ASO / HGVS Nomenclature (_184607, _184610, _184620, _184623); Transcriptome / mRNA / Spatial Transcriptomics (_184646, _184649); Mutations / Genotyping Methods / GT Safety Appendix (_184643, _184713, _184756 — incl. AAV / DRG / FDA CTGT 2021 takeaways); Proteomics / PPI / PTM (_184417, _184532, _184653, _184656); Protein Assays — LC-MS / ELISA / FRET / SIMOA / MSD / AlphaLISA / SPR (_184706, _184710); Glossary tail — Amino Acid Codes / Logarithm (_184854, _184857, _184901).

    Source Boundary / Delegation bounds against biomarkers-outcomes, mitochondria, parkin, alpha-synuclein + aSyn program entities, gba-pd-biology, gba-gcase-modalities, brain-banks-postmortem, bioorchestra-biomarker-catalog, and the sections/pk-gt-pharmacology + sections/genetics-pathway Must topics (not yet authored — disease-side AAV / GT and variant- pathogenicity ownership stays on those sections for now). The delegation table lives on the topic page; this entry does not duplicate it.

    Totals across the 18 sources: uncertain_span_count = 64 (_184532 is the only zero-uncertain-span page); embedded_image_count = 0. Per-source detail lives on the topic page; this log entry does not duplicate the Source Table. The FY21 B. KPI-linked proje… (ellipsis) versus FY21 B. KPI-linked projects (full) typo on _184857 and _184901 is preserved verbatim and the two pages remain typo-distinct first-nav_path roots in nav-path-index.

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/molecular-biology between Mitochondria and PET-Imaging.
  • log.md — this entry.

No new entity pages were created in this pass. The new topic page shares its slug stem with the pre-existing topics/by-nav/molecular- biology.md generated index, but the two paths are distinct (topics/molecular-biology.md vs topics/by-nav/molecular-biology.md) and the by-nav index is not modified. Sibling topic pages, section pages, source notes, the source catalog, the nav-path index, by-nav indexes, entity pages, and figure-asset content are not modified in this pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/molecular-biology.md (new), index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 18 specified stems from sections/molecular-biology.md. Domain-knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (pk-gt-pharmacology whole-section topic synthesis)

Whole-section topic synthesis added on top of pk-gt-pharmacology. The 11-source set covers the late-document [PK] / [PHARMACOLOGY] / [GT] / PK/PD strategy / Life-cycle / Measurement of OS / Workflow methodology chapters that the rest of the JS PD pipeline cites for small-molecule PK / PD templates, AAV cassette / capsid / promoter / dose- scaling vocabulary, ICM route-of-administration scoping, and PET-tracer Steering-Committee workflow rubrics.

Added:

  • topics/pk-gt-pharmacology.md — whole-section synthesis covering all 11 source pages assigned to sections/pk-gt-pharmacology (capture-time range 20240722_183305–20240722_184833). Five axes: PK / PD Strategy and Translational Modeling; Pharmacology — Binding Affinity / PK-PD Relationship; Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling; Route of Administration — ICM / Peripheral Leak; PET Tracer Workflow / Budget / Project Team. Source Boundary / Delegation routes program-side material to PR001 / PARKN GT / TAK-341 / SNCA ASO / SNCA BTV / aSyn Propagation Suppressor entity pages, parkin / alpha-synuclein / inflammation / gba-therapeutics, the molecular-biology § GT Safety Appendix (_184756), the cross-pipeline _184333 page on therapeutic-programs, and the disease-side OS / biomarker / PET frameworks on biomarkers-outcomes / pet-imaging. The delegation table lives on the topic page; this entry does not duplicate it. Totals across the 11 sources: uncertain_span_count = 45, embedded_image_count = 0.

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/pk-gt-pharmacology between PET-Imaging and MSA.
  • log.md — this entry.

No new entity pages were created in this pass. Sibling topic / section / source-note / source-catalog / nav-path-index / by-nav / entity / figure- asset content is not modified in this pass. _184746 retains its empty nav_path in source-note frontmatter while the section-page synthesised heading [GT] > AAV > Clinical trial / Dose Selection (visible page spans multiple headings) is preserved as authored; by-nav membership remains unclassified.

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/pk-gt-pharmacology.md (new), index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 11 specified stems from sections/pk-gt-pharmacology.md. Domain-knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (clinical-pd whole-section topic synthesis)

Whole-section topic synthesis added on top of clinical-pd. The 9-source set covers the late-document Pipeline of PD wide competitor table, two Pipeline of PD > GT methodology pages (NHP AAV9 biodistribution / ICM / intra-parenchymal route, and SV Steps / Genetics / Imaging / Readouts of synapse), the `Prodromal PD > Definition of Prodromal PD

MDS research criteria for prodromal PDreference axis, theTakeda efforts in prodromal PDPhenoconversion / P2P Platform Trial axis, theSymptom > Tx pattern WWpage, and the singleDiagnosis of PD` nav-rooted page whose visible body is the TSPO tracer table tail + CRM / Microglia structure / phenotypes chapter (nav-vs-body drift preserved as recorded).

Added:

  • topics/clinical-pd.md — whole-section synthesis covering all 9 source pages assigned to sections/clinical-pd (capture-time range 20240722_183111–20240722_184550). Six axes: Pipeline of PD — Wide Pipeline Table (GT / Cell Therapy / Inflammation / 기타 MOA들) (_184333, _184337, _184351); Gene Therapy Delivery and Synapse-Readout Methodology (_184447, _184516); Diagnosis of PD (TSPO Tracer Table Tail and Microglia Structure / Phenotypes) (_183111); Prodromal PD — MDS Research Criteria and Probability Calculator (_184404); Takeda Efforts in Prodromal PD — Phenoconversion and P2P Platform Trial (_184407); Symptom — Tx Pattern WW / Korea, Animal Model Tail, Cerevel Decision Flow, Turning, Types (_184550). Source Boundary / Delegation bounds against tak-341, parkn-gt / parkin, pr001 / gba-therapeutics, alpha-synuclein (Tier 1 + Antibody / Immunotherapy Programs axis on _184324 / _184327 / _184330 preceding _184333), therapeutic-programs § Entity Backlog Candidates (AAV2-GAD / MeiraGTx, UB-312 / Vaxxinity rows on _184333), pk-gt-pharmacology (ICM / Peripheral-leak _184443; AAV / capsid / promoter / dose-scaling vocabulary), molecular-biology § GT Safety Appendix on _184756, biomarkers-outcomes (BIOMARKER framework, MDS-UPDRS / DaTscan sample-size, RBD-as-prodromal axis, Synapse / Synaptic Change biology), and pet-imaging § Microglial Imaging — TSPO / microglia-imaging (TSPO tracer comparison table tail on _183111). The delegation table lives on the topic page; this entry does not duplicate it. Totals across the 9 sources: uncertain_span_count = 33; embedded_image_count = 2 (both on _184333 as non_text_image_assets; all other pages record 0 embeds per the 2026-04-29 body-purity decision).

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/clinical-pd between PK / PD, Pharmacology, and GT Strategy and MSA.
  • log.md — this entry.

No new entity pages were created in this pass. The AAV2-GAD / MeiraGTx and UB-312 / Vaxxinity rows on _184333 remain therapeutic-programs Entity Backlog Candidates rather than being promoted here. The new topic page shares its slug stem with the pre-existing sections/clinical-pd.md section page, but the two paths are distinct and the section page is not modified. Sibling topic / section / source-note / source- catalog / nav-path-index / by-nav / entity / figure-asset content is not modified in this pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/clinical-pd.md (new), index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 9 specified stems from sections/clinical-pd.md. Domain- knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (genetics-pathway whole-section topic synthesis)

Whole-section topic synthesis added on top of genetics-pathway. The 9-source set covers the late-document variant-pathogenicity / pathway-analysis / genetic-association / PRS / eQTL / genetic-testing / LRRK2-side Mutation chapters that the rest of the JS PD pipeline cites for methodology rather than for disease-mechanism claims.

Added:

  • topics/genetics-pathway.md — whole-section synthesis covering all 9 source pages assigned to sections/genetics-pathway (capture-time range 20240722_183404–20240722_184639). Seven axes: Variant Pathogenicity / PADD (_184314); Pathway Analysis — Tool Comparison and Worked Examples (_184317, _184509, _184320); Genetic Association Study — SNP / GATK / VCF / CNV / Gene Network (_184633); PRS, Genetic Support Level, Genetic Prevalence (_184636); eQTL, pLoF, Genetic Engineering (_184639, 4 LPS root); Genetic Testing — Multigene Panels / WES / WGS / CMA / Coverage (_184629, empty nav_path); LRRK2-Side Mutation Chapter (_183404, Mutation nav root with LRRK2-only body). Two nav-vs-body / nav-completeness states are preserved as recorded rather than reconciled: _184320 carries a Pathway Analysis > Example of Pathway Analysis > PDE nav-trail but the visible body is a PRC meeting log / PDE narrative-template page (delegated to sections/operations via the boundary table), and _184629 carries an empty nav_path and stays indexed under unclassified.

    Source Boundary / Delegation routes disease-side application to molecular-biology (HGVS / Genotyping Methods / GT Safety Appendix on _184756), biomarkers-outcomes (_184626 Synaptic change in PD HGVS / FATHMM, BMx Milestone Matrix), parkin (PRKN variants / GnomAD Genetic-prevalence application), alpha-synuclein (Carling 2020 SNCA / GCH1 / NDUFS DEG calls, SALSA P051 SNCA exon probes), gba-pd-biology / gba-gcase-modalities (GBA1 pathogenicity calls), mitochondria / lysosome-autophagy (mitochondrial / lysosomal DEG biology), inflammation / lrrk2 (LRRK2 disease-side, incl. DNL151 / DNL201), pk-gt-pharmacology / parkn-gt / snca-aso-wave / snca-btv-hdo (AAV / capsid / GT-safety application), and operations (PRC meeting-log body of _184320). The delegation table lives on the topic page; this entry does not duplicate it.

    Totals across the 9 sources: uncertain_span_count = 37; embedded_image_count = 0. Per-source detail lives on the topic page; this entry does not duplicate the Source Table.

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/genetics-pathway between Clinical PD and MSA.
  • log.md — this entry.

No new entity pages were created in this pass. The new topic page shares its slug stem with the pre-existing sections/genetics-pathway.md section page, but the two paths are distinct and the section page is not modified. Sibling topic / section / source-note / source- catalog / nav-path-index / by-nav / entity / figure-asset content is not modified in this pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/genetics-pathway.md (new), index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 9 specified stems from sections/genetics-pathway.md. Domain-knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

2026-05-03 (lysosome-autophagy whole-section topic synthesis)

Whole-section topic synthesis added on top of lysosome-autophagy (5 sources, capture-time range 20240722_183416–20240722_184542).

Added:

  • topics/lysosome-autophagy.md — whole-section synthesis covering all 5 source pages assigned to sections/lysosome-autophagy. Five axes, one per source: Lysosomal Enzymes, Transporters, and Lysosomal Changes in PD (_183416); Assessment of Lysosome — Proteolysis / pH / Hydrolytic Activity Assays (_183419); Macroautophagy / Microautophagy / CMA / BMP (_183423); Niemann- Pick Disease — NPC1 / NPC2 Typing, Pipeline, Biomarkers (_184247); TRPML1 — Activators, Tottori GD Collaboration, Pipeline (_184542). One nav-vs-body drift state is preserved as recorded rather than reconciled: _184542 carries a TRPML1 nav root while the body drifts at the bottom edge into a Catecholamine pathway → levodopa- pharmacology block that continues onto the next photo (delegated to topics/clinical-pd via the boundary table). Source Boundary / Delegation routes adjacent material across GBA-PD biology, GBA / GCase modalities, α-synuclein (CMA / KFERQ / LAMP2A / aSyn-fibril degradation), parkin (mitophagy / PINK1 / pS65-Ub), mitochondria (MAM / Complex I), inflammation / NLRP3 (PGRN-FTD CSF BMP row), LRRK2 (DNL151 / DNL201; Jennings 2022 DNL201 AHA on _183419, Denali R&D-Day LRRK2-inhibitor → BMP on _183423), pk-gt- pharmacology / molecular-biology (ETV:IDS DNL310 transcytosis vehicle, GT Safety Appendix), genetics-pathway (Carling-2020 lysosomal-DEG calls), biomarkers-outcomes, bioorchestra-biomarker- catalog, MSA, clinical-pd, therapeutic-programs (NPC / TRPML1 pipeline rows remain Entity Backlog Candidates), and operations (RD-DDU NPC / Evox correspondence on _183416); the delegation table lives on the topic page and is not duplicated here. Totals across the 5 sources: uncertain_span_count = 22; embedded_image_count = 0 (per-source detail and the Source Table live on the topic page).

Updated:

  • index.md, _sidebar.md — Topic Pages list adds topics/lysosome-autophagy between Genetics, GWAS, PRS, eQTL, and Pathway Analysis and MSA.
  • log.md — this entry.

No new entity pages were created in this pass. The new topic page shares its slug stem with the pre-existing sections/lysosome-autophagy.md section page, but the two paths are distinct and the section page is not modified. Sibling topic / section / source-note / source- catalog / nav-path-index / by-nav / entity / figure-asset content is not modified in this pass.

Verification: 0 broken wikilinks / Markdown links / image embeds across all KB Markdown files. git diff --check clean. Mutated files only: topics/lysosome-autophagy.md (new), index.md, _sidebar.md, log.md. Canonical by-photo, source-note, section-page, source-catalog, nav-path-index, by-nav-index, entity-page, figure-asset content unchanged. No raw photo / new .jpg staged. Source Table contains exactly the 5 specified stems from sections/lysosome-autophagy.md. Domain-knowledge corrections not applied; remaining Uncertain Spans preserved as review targets; external web/literature search not used.

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