JS PD KB

GBA / GCase Therapeutic Modalities

12 min read

GBA / GCase Therapeutic Modalities

Synthesis layer over the canonical by-photo corpus. This page does not replace data/processed/markdown/by-photo/. Every substantive statement links back to a source note or canonical transcription. Where the source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Bounded synthesis. This page covers the 16 source pages that build the GBA / GCase modality cluster inside gba-pd-asyn (Pipeline of GD & GBA-PD > GBA-PD > PET Imaging GBA / … > GBA Activator / … > GBA GT and their sub-leaves). It is the modality-side companion of the GBA-PD pilot (gba-pd, gba-therapeutics, biomarkers) and of the GBA / GD / GBA-PD biology synthesis (gba-pd-biology).

Overview

This page collects the corpus’s GBA / GCase therapeutic-modality block into one navigable synthesis. The 16 source pages run as one capture-time band on Page 261 / 276 / 289 / 295 / 307 / 309 of the source deck and sit between the GBA-PD biology block (closing on _182323 GBA vs UPDRS vs MOCA, owned by gba-pd-biology) and the supplement anatomy chain (_182422–_182447, section-only). Reading order is four overlapping bands: a PET Imaging GBA / modality readout bridge (MRI-GBA tail, GBA PET rationale, DDU/MJFF probe table, allosteric vs catalytic site, isofagomine, cassette / handover-to-Otake history, Catalytic-vs-Allosteric binder framing); a GBA Activator band (criteria and target profiles, RD-DDU GBA Activator, NHP Translational Model, Roche / BIAL / Gain Therapeutics competitor inventory, anti-TfR1 sdAb fusion-protein progress, RD DDU’s PET Imaging GBA feasibility plan); a GBA GT band (Executive summary cassette / D409V cassette selection, NHP studies (SNBR), TM GT GBA-PD planning matrix); and a Substrate-pathway correction band (Acid Ceramidase Inhibitor exec summary PFR-4153-100, GALC and Genetics GALC for PD, GalactosylSph (=psychosine) and Assay of GalactosylSph, Pipeline of KD, Target validation and correction). Cross-links to GBA-PD biology, the GBA-PD pilot, α-synuclein, PARKN GT, and the BioOrchestra / Brain Bank residual clusters live in § Source Boundary / Delegation.

Authoring Rules

  • No domain-knowledge corrections. The page reflects what the sources record, not what the field is “supposed” to say.
  • Uncertain Spans on the source page are preserved as uncertainty; numeric values, compound IDs, KD / IC50 ranges, dose / cassette tokens, residue numbers, and Korean inline annotations are not paraphrased.
  • The body of data/processed/markdown/by-photo/ is not modified.
  • No raw photos are staged; no new figure assets added; figure-bearing pages are linked rather than re-embedded (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md).
  • Tables on canonical pages are not re-quoted verbatim; the canonical link carries the table.
  • Out-of-scope sources (GBA-PD biology, GBA-PD pilot, α-synuclein Tier 1 + program entities, PARKN GT, supplement anatomy chain, BioOrchestra biomarker chain, Brain Bank pages) are linked, not re-narrated, per § Source Boundary / Delegation.

Source Boundary / Delegation

This topic is bounded against several sibling owners. Sources outside the 16-page set are linked from this section, not re-narrated in the axis sections.

neighbour clusterstemsowner
GBA / GD / GBA-PD biology block20240722_181813, _182123–_182146, _182153–_182323 (36 pages)gba-pd-biology
GBA-PD pilot range20240722_181748–20240722_181809 (6 pages)gba-pd, gba-therapeutics, biomarkers, eliglustat, ambroxol, venglustat, pr001
α-synuclein Tier 1 and aSyn program entitiesper alpha-synuclein-source-boundaryalpha-synuclein, tak-341, snca-aso-wave, snca-btv-hdo, asyn-propagation-suppressor
PARKN GT cross-filed page20240722_182103parkn-gt
Supplement anatomy chain20240722_182422–_182447section-only (see gba-pd-asyn)
BioOrchestra biomarker catalog (Cluster C)20240722_182708–_183115 (74 stems; _183050 excluded as α-synuclein Tier 1)bioorchestra-biomarker-catalog
Brain Bank head and standalone Brain Bank (Cluster D)20240722_182617–_182704; _184200, _184203brain-banks-postmortem

Per the program-routing map, Cluster B is the GBA / GCase modality cluster that gba-pd-biology explicitly delegates (“delegated to a future Cluster B synthesis and remains aggregated on gba-pd-asyn”). This page is that synthesis. No new entity pages are created in this pass; program-style rows on these 16 source pages (RD DDU GBA Activator, NHP Translational Model, Acid Ceramidase Inhibitor PFR-4153-100) are referenced in-axis and remain candidates for future entity promotion under therapeutic-programs Entity Backlog Candidates rather than being re-narrated as standalone program pages here.

Source Coverage

All 16 sources share the same first nav_path entry; the cluster collapses into a single nav-root row with a four-axis split below.

nav root (first nav_path entry)sourcescovered axis
Pipeline of GD & GBA-PD16PET Imaging GBA / modality readout bridge (3) · GBA Activator (5) · GBA GT (3) · Substrate-pathway correction — Acid ceramidase / GALC / GalactosylSph / Pipeline of KD / Target validation (5)
total16

Across these 16 sources, the source-note frontmatter records 14 uncertain_span_count entries and 0 body-embedded figure assets — review surface area, not resolutions. The zero-figure-embed count reflects the 2026-04-29 body-purity decision: figure-bearing crops on these pages (Probe table, Cassette-selection cartoons, Lysosome cartoons, Allosteric / Catalytic site diagrams) are kept as evidence at the canonical level rather than re-embedded here.

PET Imaging GBA — Modality Readout Bridge

Three pages bridge the biology block (closing on _182323, owned by gba-pd-biology) into the GBA Activator / GBA GT modality bands by carrying the MRI-GBA tail and the GBA PET program’s framing (rationale, allosteric-vs-catalytic site, isofagomine, DDU/MJFF probe panel, Otake handover).

  • PET Imaging GBA (MRI tail + Progress so far). MRI-GBA closing rows and the GBA PET binder workstream (allosteric vs catalytic site framing, isofagomine reference, FRET / ASMS binder panels) (md, 0 uncertain spans). Cell values, compound IDs, and KD / IC50 ranges remain on the canonical page.
  • PET Imaging GBA (history, Otake handover, GBA GT reporter). Handover-to-Otake-san plan, catalytic-vs-allosteric binder framing for the Paul 20200825 meeting, and the GBA GT reporter system hand-off (md, 1 uncertain span on the competitor-on-radar row).
  • PET Imaging GBA > GBA Activator (rationale → criteria handoff). AADC PET tail, Rationale of GBA PET, GBA-expression Go/No-Go diagram, DDU/MJFF probe context, and the GBA Activator PRC1 cross- site meeting visual flow that opens the next axis (md, 2 uncertain spans). The nav_path transitions from PET Imaging GBA to GBA Activator on this page.

GBA Activator — RD-DDU, NHP Translational Model, Competitor / Fusion Protein, RD DDU’s PET Imaging GBA

Five pages cover the GBA Activator modality and its RD-DDU / translational / competitor / fusion-protein / PET-imaging branches under Pipeline of GD & GBA-PD > GBA-PD > GBA Activator.

  • GBA Activator > RD-DDU GBA Activator. Activator criteria, GBA-activity / GlcSph-reduction split, the L444P Lyso-GL1 substrate result, and the GBA GT executive-summary lead-in (md, 2 uncertain spans).
  • GBA Activator > NHP Translational Model. Tx Paradigm, the Biomarker Usage Map for GBA activator in PD (Takeda), DMPK PK/PD questions across Genetics / Translational / Biomarker / Clinical trial axes, and the tempo code 43/6-100 Executive summary opener (md, 1 uncertain span).
  • GBA Activator > Competitor. GCB BTV Executive summary, Biodistribution Studies, Comp Bio notes, and the competitor inventory (Roche GCB BTV; BIAL AGN-242647 / LTI-291 / ACTIVATE) with the GBA activation table (md, 1 uncertain span). Continues onto the Fusion Protein page.
  • GBA Activator > Competitor > Fusion Protein. BIAL LTI-291-004 tail, Gain Therapeutics GT-02287, and the anti-TfR1 sdAb fusion protein program (GCB variants, in-vivo plan, 001 PE preparation feedback) (md, 0 uncertain spans).
  • GBA Activator > RD DDU’s PET Imaging GBA. GCB PET vs Lysosomotropic PET feasibility / BD / pharmacological-modulation plan and sample-size estimation for the natural-history and pharmacological branches (md, 0 uncertain spans). Closes the RD-DDU PET-imaging plan opened on the modality readout bridge.

GBA GT — Executive Summary, NHP Studies (SNBR), TM GT GBA-PD

Three pages cover the GBA gene-therapy modality under Pipeline of GD & GBA-PD > GBA-PD > GBA GT — the preclinical-to- translational arc anchoring cassette / dose / model selection, PK-PD and immunogenicity, and patient-selection planning.

  • GBA GT > Executive summary. STIG1 cassette-selection criterion, the 7-group D409V homozygous rAAV9 / ICV cassette-selection study, PRC1 submission, the GbaD409V/D409V KI homo GD mouse model, and the 4L/PS PD mouse model schedule (md, 2 uncertain spans on cassette / PE-schedule rows).
  • GBA GT > NHP studies > SNBR (Shin Nippon Biomedical Laboratories). PK-PD strategy, immunogenicity-assay PRC1, and the NHP study with SNBR as in-vivo CRO (Sacral DRG / HA staining) (md, 0 uncertain spans).
  • GBA GT > TM GT GBA-PD. TM GT GBA-PD planning matrix (stratification rows, patient-selection / BM-discovery matrix, Rebecca / vMRI / GBA PET / GBA protein & mRNA / GBA pathway columns) (md, 0 uncertain spans). MC1-PET tracer-development context for the GBA PET column is delegated to mitochondria / pet-imaging and is not re-narrated here.

Substrate-Pathway Correction — Acid Ceramidase, GALC, GalactosylSph, Pipeline of KD, Target Validation

Five pages cover the substrate-pathway correction strand — neighbouring lipid-substrate enzymes (Acid Ceramidase, GALC) and their disease- state correlates (Farber lipogranulomatosis, Krabbe’s Disease) — under Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > … sub-leaves.

  • GBA Activator > Acid ceramidase inhibitor. Acid Ceramidase Inhibitor — Executive summary (Yuta) (program code PFR-4153-100), the AC enzyme-pathway substrate / product panels, and the Genetics ASAH1 / Farber lipogranulomatosis row (md, 1 uncertain span).
  • GBA Activator > GALC > Genetics GALC for PD. IPDGC LSD-Gene- Variants Supplementary Table 3 (ASAH1), the Cf) CADD C-Score reference, the GALC enzyme block, and Genetics GALC for PD (md, 2 uncertain spans).
  • GBA Activator > GalactosylSph (=psychosine) > Assay of GalactosylSph. NIH ClinVar GALC tail, GalactosylSph substrate block, Disease state comparison, the Assay of GalactosylSph block, and the Krabbe’s Disease (=Globoid cell leukodystrophy) opener (md, 1 uncertain span). The aSyn / Krabbe relationship note on this page is treated as a cross-link to alpha-synuclein only, not re-narrated here.
  • GBA Activator > Pipeline of KD > Target validation and correction. Pipeline of KD, MOA for PD, the AC Inhibitor monthly reports, Safety / Safety BM, and the Target-validation-and- correction subsection opener (md, 1 uncertain span).
  • GBA Activator > Target validation and correction > 총정리중 GBA+PD에서 Lys. Kim 2018 #1185 carmofur GBA-KO row (Figure 7 / Figure 8 callouts kept canonical), GBAL444P/L444P iPSC-DAn results, patient-segmentation questions, and the GALC enzyme summary that closes the band (md, 0 uncertain spans). Page-header 총정리중 GBA+PD에서 Lys Korean annotation preserved verbatim.

Source Table

Provenance ground-truth for the 16 sources, in capture-time order.

stemnav path / headingsource notecanonicaluncertain spansembedded images
20240722_182326Pipeline of GD & GBA-PD > GBA-PD > PET Imaging GBAnotemd00
20240722_182330Pipeline of GD & GBA-PD > GBA-PD > PET Imaging GBAnotemd10
20240722_182333Pipeline of GD & GBA-PD > GBA-PD > PET Imaging GBA > GBA Activatornotemd20
20240722_182336Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > RD-DDU GBA Activatornotemd20
20240722_182339Pipeline of GD & GBA-PD > GBA-PD > GBA GT > Executive summarynotemd20
20240722_182343Pipeline of GD & GBA-PD > GBA-PD > GBA GT > NHP studies > SNBR (Shin Nippon Biomedical Laboratories)notemd00
20240722_182346Pipeline of GD & GBA-PD > GBA-PD > GBA GT > TM GT GBA-PDnotemd00
20240722_182351Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > NHP Translational Modelnotemd10
20240722_182355Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > Competitornotemd10
20240722_182358Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > Competitor > Fusion Proteinnotemd00
20240722_182402Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > RD DDU’s PET Imaging GBAnotemd00
20240722_182406Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > Acid ceramidase inhibitornotemd10
20240722_182409Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > GALC (galactosylceramidase) > Genetics GALC for PDnotemd20
20240722_182412Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > GalactosylSph (=psychosine) > Assay of GalactosylSphnotemd10
20240722_182416Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > Pipeline of KD > Target validation and correctionnotemd10
20240722_182419Pipeline of GD & GBA-PD > GBA-PD > GBA Activator > Target validation and correction > 총정리중 GBA+PD에서 Lysnotemd00

Totals across the 16 sources: uncertain_span_count = 14; embedded_image_count = 0. Per-axis subtotals:

  • PET Imaging GBA / modality readout bridge (3 pages): 3 uncertain spans, 0 embedded images.
  • GBA Activator (5 pages): 4 uncertain spans, 0 embedded images.
  • GBA GT (3 pages): 2 uncertain spans, 0 embedded images.
  • Substrate-pathway correction (5 pages): 5 uncertain spans, 0 embedded images.

Numbers are review surface area, not resolutions.

Uncertainties Carried Forward

Uncertainty hot spots worth checking before downstream extraction. The page does not paraphrase uncertain content; open the canonical page for cell values.

  • PET Imaging GBA bridge (_182330 1, _182333 2 uncertain spans). The PET-history → Otake-handover → GBA-Activator-PRC1 rationale handoff carries the densest uncertainty on the bridge axis (in-vitro / in-vivo criterion cells, competitor-on-radar row).
  • RD-DDU GBA Activator preclinical anchor (_182336, 2 uncertain spans). L444P Lyso-GL1 substrate result table; the page-margin Korean annotation wt 없네? is preserved verbatim on the canonical page.
  • GBA GT Executive summary cassette / D409V selection (_182339, 2 uncertain spans). Cassette-selection rows, MOI definition, PRC1 submission, and the 4L/PS / CBE+A53T / CBE+Line 83 PE schedule carry the densest uncertainty in the GBA GT axis.
  • GBA Activator NHP TM and Competitor (_182351 1, _182355 1 uncertain span). DMPK PK/PD with the tempo code 43/6-100 opener and the Roche / BIAL competitor inventory carry inline uncertainty on identifiers and trial-table cells.
  • Substrate-pathway correction (_182406 1, _182409 2, _182412 1, _182416 1 uncertain spans). Acid Ceramidase Inhibitor (PFR-4153-100) AC-pathway directionality, GALC IPDGC LSD-variant table and Cf) CADD C-Score, GalactosylSph Disease state comparison, and the Pipeline-of-KD / AC-Inhibitor monthly report rows are the substrate-axis hot spots.

그래프 뷰

백링크