PK / PD, Pharmacology, and GT Strategy

This topic page reorganises the 11 source notes filed under pk-gt-pharmacology into reading-order axes. It does not replace the by-photo Markdown; every claim links back to a source note or the canonical transcription. Where a source carries Uncertain Spans, that uncertainty is preserved here rather than smoothed out.

Overview

The corpus treats PK / PD, pharmacology, and gene-therapy strategy as a single methodology-side reference block — late-document chapters whose dose-PK-PD- efficacy templates, AAV cassette / capsid / promoter / route taxonomies, and PET-tracer / Steering-Committee workflow rubrics are imported by the disease- side program pages. Five reading-order axes organise the 11 sources: PK / PD strategy and translational modeling (small-molecule PK/PD with an NLRP3i worked example and a Beloranib reference-drug pair); pharmacology — binding affinity and PK-PD relationship (enzyme-inhibitor types and the Parameters of PET ligand HDAC6 worked example); gene therapy — AAV cassette / capsid / promoter / manufacturing / dose-scaling; route of administration — ICM / peripheral leak; and PET-tracer workflow / budget / project-team function table. Per- program PK/PD models, capsid / promoter / cassette selections, dose / route choices, and PET biomarker plans live on the relevant entity / topic pages and are only linked here; this page does not re-narrate them.

Source Boundary / Delegation

This topic is bounded inside sections/pk-gt-pharmacology and does not include sources from sibling sections. Adjacent material that overlaps but is owned elsewhere:

boundary	owned by
PARKN GT (PFR-4249-100) AAV9-Parkin GT preclinical / clinical material	parkn-gt / parkin
PR001 (LY3884961) AAV / GBA GT (CBE / 4L/PS-NA / A53T+CBE / NHP ICM / PROPEL FIH)	pr001 / gba-therapeutics
TAK-341 / MEDI1341 antibody PK/PD model and clinical studies	tak-341 / alpha-synuclein
SNCA ASO (WAVE) PK/PD in A53T mice and clinical plan	snca-aso-wave / alpha-synuclein
SNCA BTV (HDO) (PFR-4067-100) program plan and HDO PET Development Workflow	snca-btv-hdo / alpha-synuclein
aSyn Propagation Suppressor (aSyn Programs umbrella)	asyn-propagation-suppressor / alpha-synuclein
AAV / GT safety appendix on _184756 (Re-dosing / Route / Seroepidemiology / DRG Toxicity / FDA CTGT 2021)	molecular-biology § Mutations / Genotyping Methods / GT Safety Appendix
NLRP3-inhibitor program PK/PD (TR06673219 is the methodology worked example only on _183305)	inflammation / nlrp3-inhibitor
Pipeline-of-PD GT row continuation on _184333 (AAV2-GAD / MeiraGTx, UB-312, MEDI1341 SAD continuation)	clinical-pd / therapeutic-programs
α-synuclein biology / aSyn pathology (Tier 1)	alpha-synuclein
Disease-side OS / biomarker validation; PET tracer-development framework	biomarkers-outcomes / pet-imaging

Source Coverage

11 source notes are assigned to the pk-gt-pharmacology section. They sit across 10 first-level nav_path clusters (one source — _184746 — has no recorded nav_path and is treated as Unclassified in unclassified); the topic axes below collapse those clusters as follows:

nav root (first nav_path entry)	sources	covered axis
PK/PD	1	PK / PD Strategy and Translational Modeling
[PK]	2	PK / PD Strategy and Translational Modeling
[PHARMACOLOGY]	1	Pharmacology — Binding Affinity / PK-PD Relationship
Units (dose and transgene…)	1	Pharmacology — Binding Affinity / PK-PD Relationship
(Unclassified — no nav_path)	1	Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling
Life-cycle	1	Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling
PK/PD strategy	1	Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling
Study population	1	Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling
Measurement of OS	1	Route of Administration — ICM / Peripheral Leak
Workflow	1	PET Tracer Workflow / Budget / Project Team

For exact nav_path strings and headings see pk-gt-pharmacology and the matching by-nav indexes listed in related_topics_by_nav. _184746 has an empty nav_path in source-note frontmatter; the section page synthesises a heading [GT] > AAV > Clinical trial / Dose Selection (visible page spans multiple headings) for clustering, and the by-nav membership remains unclassified. Both are preserved as recorded.

Across the 11 sources, source-note frontmatter records 45 uncertain_span_count entries and 0 body-embedded figure assets. The zero embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md); mixed text-and-figure crops on these pages are kept as evidence at the canonical by-photo level rather than embedded. The 45 uncertain spans are retained as review targets and not resolved here.

PK / PD Strategy and Translational Modeling

20240722_183305 opens PK/PD > PK/PD Strategy with a CNS1 / CNS2 / Peripheral PK/PD worked-example matrix anchored on the NLRP3 inhibitor TR06673219, plus MOUSE Free Brain Exposure / HUMAN Free Brain Target mini-tables, a Postmortem / Proteina tail, and several Takeda-branded PK/PD slide thumbnails kept as evidence. 5 Uncertain Spans. The disease-side NLRP3-program PK/PD context is owned by inflammation / nlrp3-inhibitor; this page treats TR06673219 as the methodology-side worked example only.

20240722_184716 is the [PK] > Parameters > Dose-PK-PD-Efficacy relationship in Vivo template page (Below LOD Olink strategies, AUC / AUC24 / AUCtau definitions, and the Farrell 2019 PMID 31537613 %BWL worked example). 4 Uncertain Spans. 20240722_184720 continues the chain under Translational modeling (and prediction of clinical efficacy) using a reference drug (that has clinical data), with the Beloranib DIO Efficacy / Translational PK/E Model / Receptor-Occupancy / Exposure-vs- Occupancy panels and JS asides preserved verbatim. 4 Uncertain Spans. The two pages should be read as one Dose-PK-PD-Efficacy template; per-cell values stay on the source pages.

Pharmacology — Binding Affinity / PK-PD Relationship

20240722_184802 walks the [PHARMACOLOGY] > Binding Affinity > PK-PD relationship enzyme-inhibitor comparison table (Competitive / Non-competitive / Uncompetitive / Mixed / Irreversible) with <mark>venglustat</mark> as the uncompetitive worked example, then opens Binding Affinity, PD relationship, and the time course of effects: three scenarios (Holford 2017) block. 4 Uncertain Spans.

20240722_184806 is the Parameters of PET ligand HDAC6 worked example (Antibody radiolabelling sub-table, 4-column parameter / description / Criteria / HDAC6 matrix with Bmax assessment in rats and Friden f_u,b slide screenshots and the MDR1 efflux-ratio schematic kept as evidence). 5 Uncertain Spans.

20240722_184759 bridges the GT and Pharmacology axes: a Below from Parkin GT LGE slidedeck Potential-Safety-Issue four-row template (Immunogenicity Capsid / Transgene, Cellular stress/cytotoxicity, Genotoxicity), the Study population HV counterargument, the Type of gene therapy three-category table, the Units (dose and transgene expression) matrix (미보고 / 미구분 cells preserved verbatim), and the [PHARMACOLOGY] Binding sub-table opener that continues into _184802. 4 Uncertain Spans. The PARKN GT program-specific safety / de-risking detail lives on parkn-gt.

Gene Therapy — AAV / Cassette / Promoter / Manufacturing / Dose Scaling

20240722_184746 is the AAV-cassette / capsid / clinical-trial / dose-selection / glossary page (empty nav_path in source-note frontmatter; section-page synthesised heading [GT] > AAV > Clinical trial / Dose Selection (visible page spans multiple headings)). It carries the AAV / capsid receptor notes, the 6- column Cassette-structure schema, the Gene Therapy Approach for GBA-PD slide, the Clinical trial Early / Late and Luxturna-by-Spark example, the Dose Selection Traditional-allometric / Starting-dose-FIH / Dose-escalation / Max-dose templates, and a Glossary block. 5 Uncertain Spans.

20240722_184749 is the Life-cycle > Localization > Manufacturing > PK/PD strategy page (Adenovirus / AAV viral-entry life-cycle, AAV genome map Figure 1, the Immunosupressnats (sic) wide IS in Intrathecal / Intracisternal AAV Programs table comparing AAVRH10-SOD1 / scAAV9/JeT-GAN / Lacerta Pompe / Zolgensma SMA2 regimens, plus a closing PK/PD matrix that continues below the photo crop). 4 Uncertain Spans.

20240722_184753 is the PK/PD strategy > Dose Scaling for GT > Promoter page (GT PK comparison continuation across Hunter TAK-073 / Fabry / hemophilia, the Dose_Human = Dose_Animal · Scaling factor · Activity factor equation with mouse-to-human / NHP-to-human activity-factor highlights preserved verbatim, the Species-difference analyte matrix, and the start of Table 1 on Promoters). 4 Uncertain Spans.

_184759 (also covered under the Pharmacology axis above) carries the Parkin-GT-LGE Potential-Safety-Issue four-row template, the DRG-pathology 33-NHP-study meta-analysis paragraph, and the Type of gene therapy / Units (dose and transgene expression) matrices before handing off to _184802. The disease-side AAV / DRG / FDA CTGT 2021 takeaways live in molecular-biology § Mutations / Genotyping Methods / GT Safety Appendix (_184756); program-specific PARKN GT safety / bioanalytical content lives on parkn-gt.

Route of Administration — ICM / Peripheral Leak

20240722_184443 is the `Measurement of OS > Route of Administration > ICM (= Suboccipital puncture)

Peripheral leak/transductionpage. It carries an upper-body OS / Redox- state / 8-OHdG / 7β-HCMeasurement of OSsummary table (the disease-side OS / biomarker validation chain stays on [[biomarkers-outcomes|topics/biomarkers-outcomes]]) and then the ICM section proper: theIntra-cisterna magna (ICM) injectionclinical-indication summary table (Tay-Sachs Sandhoff's through Krabbe rows), two anatomical line drawings kept as evidence, and the Hauricot 2013 #1613 dog AAV9-GFP biodistribution table whose ~2018-dog bar chart continues onto_184456. 3 Uncertain Spans`.

PET Tracer Workflow / Budget / Project Team

20240722_184833 is the Workflow > Budget/Responsibilities page (HDAC6 [18F]EKZ-001 Clinical PET Protocol cohort A / B / C continuation, Success-criteria row, the green Evaluation of ligand candidates in human ICH M3 (R2) bullet box, the Talvik 2002 receptor-occupancy FIG.9.1 kept as evidence, the Budget/Responsibilities wide table with General / NLRP3 / Mil$ / Parkin GT columns, and the start of the Project Team — Function Table). 3 Uncertain Spans. The disease-side PET tracer-development framework is owned by pet-imaging; program-specific PET budget and biomarker plans (PARKN GT MC1 PET, NLRP3i [18F]DPA714 / [18F]FEPPA) live on the relevant entity / topic pages.

Source Table

All 11 sources, in capture-time order, with the per-page uncertain-span and embedded-image counts copied verbatim from source-note quality_metrics. nav path is the full nav_path recorded in the source note.

stem	nav path / heading	source note	canonical	uncertain spans	embedded images
20240722_183305	PK/PD > PK/PD Strategy	note	md	5	0
20240722_184443	Measurement of OS > Route of Administration > ICM (= Suboccipital puncture) > Peripheral leak/transduction	note	md	3	0
20240722_184716	[PK] > Parameters > Dose-PK-PD-Efficacy relationship in Vivo	note	md	4	0
20240722_184720	[PK] > Parameters > Dose-PK-PD-Efficacy relationship > Translational modeling (and prediction of clinical efficacy) using a reference drug (that has clinical data)	note	md	4	0
20240722_184746	(no nav_path recorded; section-page heading: [GT] > AAV > Clinical trial / Dose Selection (visible page spans multiple headings))	note	md	5	0
20240722_184749	Life-cycle > Localization > Manufacturing > PK/PD strategy	note	md	4	0
20240722_184753	PK/PD strategy > Dose Scaling for GT > Promoter	note	md	4	0
20240722_184759	Study population > Type of gene therapy > Units (dose and transgene expression) > [PHARMACOLOGY]	note	md	4	0
20240722_184802	Units (dose and transgene…) > [PHARMACOLOGY] > Binding Affinity > PK-PD relationship	note	md	4	0
20240722_184806	[PHARMACOLOGY] > Binding Affinity > PK-PD relationship	note	md	5	0
20240722_184833	Workflow > Budget/Responsibilities	note	md	3	0

Totals across the 11 sources: uncertain_span_count = 45, embedded_image_count = 0. These are review surface area; the zero-figure- embed count reflects the 2026-04-29 body-purity decision (docs/decisions/2026-04-29-body-purity-and-figure-only-embeds.md) under which mixed text-and-figure crops on these pages are kept as evidence rather than embedded.

Uncertainties Carried Forward

Hot spots worth checking before any downstream extraction; per-cell values stay on the canonical by-photo pages and are not paraphrased here:

• PK / PD Strategy and Translational Modeling: image-primary RO(%) and FreeBrain_human = FreeBrain_mouse * (IC50_human / IC50_mouse) formulas on _183305; the BWL Panel B chart on _184716 ends mid-axis and continues onto _184720; JS asides on _184720 preserved verbatim.
• Pharmacology / PK-PD: the <mark>venglustat</mark> highlight and the red- text caveat block on _184802; the Bmax & Kd continuation paragraph on _184806 ends mid-page and crosses to _184809; the Middle* token (asterisk preserved) in the Parkin-GT-LGE Immunogenicity (Transgene) Probability cell on _184759.
• Gene Therapy: _184746 nav_path is recorded empty in source-note frontmatter while the section page synthesises a [GT] > AAV > Clinical trial / Dose Selection (visible page spans multiple headings) heading (intentionally not reconciled); Immunosupressnats heading typo and the JS aside 이것 이상함, AAVs don't replicate! on _184749 preserved verbatim; <mark>vg/kg</mark> highlights and the Activity-factor purple- box yellow highlights on _184753 preserved verbatim.
• Route of Administration: the ~2018-dog bar chart on _184443 continues onto _184456.
• PET Tracer Workflow: the <mark>...</mark> highlights and the red-text / yellow-highlight PJ-TML token in the Project-Team blue band on _184833.
• Page-label denominator drift across the late-document chapters (_184716 Page 1229 of 1238 vs _184720 of 1239; _184759 Page 1273 of 1282 vs _184802 of 1284) is a Word-status-bar artifact and is preserved as recorded.

Related Pages

• pk-gt-pharmacology — section index for all 11 sources
• molecular-biology — sibling topic; § Mutations / Genotyping Methods / GT Safety Appendix on _184756 carries the AAV / DRG / FDA CTGT 2021 takeaways that this topic does not include, and § Protein Assays anchors the [Protein] > Assays LC-MS / ELISA / FRET / SIMOA / MSD / AlphaLISA / SPR vocabulary that the Parameters of PET ligand HDAC6 page on _184806 re-uses
• parkin — sibling topic; per-program PARKN GT decision tree, biomarker matrix, NHP plan, bioanalytical method, sample-size logic, PE I Imaging GBA plan, TM Assays
• alpha-synuclein — sibling topic (Tier 1); aSyn programs umbrella and per-program TAK-341 / SNCA ASO / SNCA BTV / aSyn Propagation Suppressor PK/PD / dose / route content
• gba-therapeutics / gba-pd — sibling topics; GBA-PD pilot per-compound (Eliglustat / Ambroxol / Venglustat) and PR001 AAV9-GBA gene-therapy detail
• inflammation — sibling topic; NLRP3 inhibitor TR06673219 PK/PD program scope and series-5c chemistry detail
• pet-imaging — sibling topic; PET / tracer-development / DATscan / VMAT-2 / immunoPET disease-side framework that the HDAC6 [18F]EKZ-001 and Talvik 2002 receptor-occupancy methodology pages here support
• biomarkers-outcomes — sibling topic; disease-side OS / biomarker / outcome-measure validation chain that consumes the Measurement of OS redox / 8-OHdG / 7β-HC vocabulary on _184443
• therapeutic-programs — program-routing map (PR001, PARKN GT, NLRP3i, TAK-341, SNCA ASO, SNCA BTV, aSyn programs umbrella) that depends on the dose-scaling / capsid / promoter / route vocabulary defined here
• pr001 / parkn-gt / tak-341 / snca-aso-wave / snca-btv-hdo / asyn-propagation-suppressor — program entities that consume the AAV / capsid / promoter / dose-scaling / route-of-administration / PET-ligand / Steering-Committee / Budget vocabulary defined here
• pk — [PK] first-nav_path index
• pk-pd — PK/PD first-nav_path index
• pk-pd-strategy — PK/PD strategy first-nav_path index
• pharmacology — [PHARMACOLOGY] first-nav_path index
• units-dose-and-transgene — Units (dose and transgene…) first-nav_path index
• study-population — Study population first-nav_path index
• life-cycle — Life-cycle first-nav_path index
• measurement-of-os — Measurement of OS first-nav_path index
• workflow — Workflow first-nav_path index
• gt — [GT] first-nav_path index (no pk-gt-pharmacology source has [GT] as its first nav_path entry — _184746 has an empty nav_path and the section-page synthesised heading prefixes [GT] only as a clustering aid; this index is linked because the GT axis re-uses the same vocabulary)
• unclassified — generated index for sources whose nav_path is empty (includes _184746)
• source-catalog — all 447 sources in capture order
• nav-path-index — 376 distinct nav_paths