Multiple System Atrophy (MSA)

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.

Authoring Rules

• No domain-knowledge corrections; reflect what the sources record.
• Uncertain Spans content is left as uncertainty and is not paraphrased into definitive prose.
• Tables on canonical pages are linked, not re-quoted.
• The α-synuclein Tier 1 page 20240722_184156 (`MSA > aSyn in MSA

  CSF aSyn in MSA`) is owned by alpha-synuclein per the boundary map; this page does not re-narrate it.

Overview

The MSA arc collects nine pages across two first-nav_path clusters (MSA 7, Pipeline MSA 2). It groups into six reading-order axes: (1) the Gilman 2008 three-level diagnosis framework (20240722_184206, 20240722_184210); (2) UMSARS / MSA-QoL / ICLEMSA outcome measures and the MSA NfL longitudinal / cross-sectional biomarker tables (20240722_184216, 20240722_184219); (3) MSA pathology and subtype comparison (20240722_184219, 20240722_184223, 20240722_184230, 20240722_184233); (4) the Pipeline MSA disease-modifying / symptomatic asset table (20240722_184223, 20240722_184226, 20240722_184230); (5) cohort / natural-history (NAMSA-SG, EMSA-SG, TALISMAN, P+A+MS) (20240722_184206); (6) the RBD-as-MSA-prodrome page reached via the Pipeline MSA > Disease-modifying > RBD screening question… nav-root (20240722_184430), plus a TM in MSA > Mucolipidosis (ML) cross-reference (20240722_184233).

Source Coverage

nav root (first nav_path entry)	sources	covered axis
MSA	7	Diagnosis, Genetics / In vitro / Imaging / DATscan, UMSARS / MSA-QoL / ICLEMSA, NfL CSF and blood, Pathology and subtype comparison, Pipeline MSA disease-modifying, TM in MSA > Mucolipidosis (ML) cross-reference
Pipeline MSA	2	KM-819 / IkT-148009 continuation; Key Ongoing Trials Gantt; Symptomatic table; Subtype clinical and Figures 1 / 3; Prevalence; RBD screening (RBDSQ family) and RBD mechanism / pathology / animal model / GBA → RBD
total	9

Across these 9 sources, source-note frontmatter records 29 uncertain_span_count entries and 0 body-embedded figure assets — review surface area, not resolutions. The zero-embed count reflects the 2026-04-29 body-purity decision under which mixed text-and-figure crops on these pages (the Lu AF82422 Phase 2 → Phase 3 Bayesian-adaptive timeline diagram, the SRM bar chart and Tables 4 / 5 on _184219, the Key Ongoing Trials Gantt and Figures 1 / 3 / brainstem-nuclei schematics on _184230, the brain-anatomy schematic and MLIV disease-progression curve on _184233, and the Bridel / Hansson / Ashton / Palleis NfL plots on _184216) are kept as evidence rather than embedded.

Diagnosis of MSA — Gilman 2008 Three-Level Criteria

The MSA diagnostic framework is the Gilman et al. 2008 (PMID 18725592) Second consensus statement, reproduced as a colour- banded Possible / Probable / Definite table on md and again on md, where the same table is followed by plain-prose criteria for Probable MSA, Possible MSA, the additional-features list (Babinski / Stridor; MSA-P; MSA-C variants), and the Definite row anchored on Autopsy findings of widespread and abundant CNS aSyn–positive glial cytoplasmic inclusions. Both pages preserve the prose Possible MSA-C block ending mid-sentence at Presynaptic nigrostriatal dopaminergic … (the colour panel above carries the full bullet); re-check the canonical page rather than reconciling here.

Genetics, In Vitro Systems, Imaging, and DATscan

md clusters four sub-blocks under Dx of MSA:

• Genetics. Reference-table rows for {Stankovic, 2019 #1649} COQ2 mutations and GCTA-derived MSA heritability, {Wernick, 2020 #2585} GBA-variant association in 167 pathology-confirmed MSA cases (driven by p.T408M, with the conclusion that other coding GBA variants are not associated), and {Sklerov, 2017 #2586} 17-autopsy GBA-variant frequency vs pure-AD comparator. Cell values, OR / P numerics, and the duplicated Stankovic, 2019 #1649} brace artefact are retained on the canonical page.
• In vitro systems. A {Abati 2018 #2279} opener feeds a five-row Stefanova / oligodendroglial / iPSC-derived oligodendrocyte table whose Authors column is clipped at the left edge for four of five rows (…ragh et al (2009), …ay et al (2014), …alera et al (2017), …elloul et al (2015)); flagged uncertain.
• Imaging. Stankovic 2019 #1649 paragraph on conventional MRI and FDG-PET signs in putamen / MCP / pons / cerebellum, DWI / advanced MRI improvement of early-stage diagnostic accuracy, the early-MSA-P pattern of posterior-putamen / MCP diffusivity and putamen / cerebellar volume loss, the 123I-metaiodobenzylguanidine–SPECT myocardial sympathetic supporting feature, and the open caveat that cutaneous α-syn diagnostic characteristics are not definitively established. The footnote glyph reads 3) and may be footnote 33 — preserved as written.
• DATscan. A {Nocker, 2012 #1075} two-period planning table (8 MSA-P / 11 sPD; Brainstem and Striatum cross-sectional vs 1.3y후 columns) and the follow-on Calculated sample sizes table (effect size 20% / 33% / 50% × Striatum / Putamen / Caudate); cell values are on the canonical page.

Outcome Measures — UMSARS, MSA-QoL, and ICLEMSA

• UMSARS structure is unchanged since Wenning et al. 2004 (PMID 15452868) and consists of four sub-scales (Historical Review 12 items, Motor Examination 14 items, Autonomic Examination 4 items, Global Disability 1 item); per-item lists are on md. The page records the TAK-341 IDP anchor 5 (10.4) point difference vs. placebo (Poewe et al. 2015) against the Historical Review scale. Higher scores = more severe disease; administration time ~15 min (Palma, 2021 #1633).
• UMSARS progression and sample size. {Wenning, 2013 #1077} records 24-month progression rates (ADL 49%, motor 74%, total 57% relative to baseline; absolute SD-bracketed values on the canonical page), the predictors of rapid UMSARS progression (shorter symptom duration, absent levodopa response), and the per-EMSA-SG sample-size estimate that 258 patients (129 / group) would detect a 30% effect size in 1-year UMSARS motor decline at 80% power (md).
• MSA-QoL. Original {Schrag, 2007 #1503}; example {Matsushima, 2021 #1389}. The source records the JS aside , 그런데 questionnaire 자체는 안 구해지네, MDS site 에도 안 보이는 듯? (md).
• ICLEMSA — Items That Change Largely in Early-Stage Multiple System Atrophy. Eight-item provisional scale assembled from UMSARS (handwriting, finger tapping, body sway), SARA (gait), and BBS (transfers, feet-together standing, looking-behind, 360° turn). Development cohort was MSA-C-dominant (29.4% MSA-P / 70.6% MSA-C). The Matsushima 2016 #1447 SRM6 / SRM12 bar chart (preserved as evidence), Table 4 (per-item grading), and Table 5 (required sample size per scale at 80% power, 30% effect, two-sided α=0.05) live on md; the yellow-highlighted provisional-scale value (98) is the page’s anchor for ICLEMSA’s sample-size advantage over full-UMSARS. The canonical page records the JS aside that handwriting 은 Palma에서도 고순위인데, finger tapping & body sway 는 Palma 에서 X — the author flags a partial scale- validity disagreement that is preserved as written.

NfL Biomarker — CSF and Blood, Cross-Sectional and Longitudinal

md carries two stacked NfL tables under NfL in MSA:

• Longitudinal NfL. Five rows: Palma 2022 (Kaufmann lab) sirolimus / rapamycin study (N=12, plasma SIMOA, UMSARS-vs-NfL correlation r=0.732, P=0.006 total / r=0.795, P=0.002 for UMSARS-2 with the JS planning aside but we need a slowing-based estimation?); Tokutake et al CSF MSD R-PLEX (N=10, source- highlighted 감소 trend 네? and r=0.8863, P=0.0013 baseline- vs-UMSARS2-change); Zhang 2021 plasma SIMOA (N=64); Petzold 2009 CSF ELISA (source-highlighted No change over 12 months); Constantinesu 2010 CSF ELISA (N=14 MSA-P / N=7 MSA-C — the surname is preserved without correction).
• Cross-Sectional and Longitudinal CSF / Blood. (Bridel, 2019 #1407) CSF meta-analysis fold-change vs HC and a flat yearly- increase signal (-0.68 (-2.03-0.69), ns), and a yellow- highlighted Korean JS note that the four CSF longitudinal studies show no clear increase / decrease — axonal secreton/neuronal loss 가 서로 상쇄하나 보다. Blood cross-sectional {Hansson, 2017 #1691} Lund / London / early-disease cohorts (the source’s n 5 278 / n 5 117 glyph is preserved as written) showing elevated blood NfL across all APD groups vs PD and HC; {Ashton, 2021 #1692} King’s College London + BioFINDER cohorts (MSA n=29); {Palleis, 2020 #1693} blood-longitudinal N=1 with strong UMSARS correlation. Per-row cell values, plot anchors, and the four embedded plot crops live on the canonical page and are not re-quoted.

Pathology and Subtype Comparison

The pathology block spans md (Inclusions table), md (Cell loss / Aβ / tau / DeMyelination / microgliosis / splice rows), and md (subtype comparison; TM in MSA).

• Inclusions. GCI (Papp-Lantos bodies) in oligodendrocytes are mandatory for diagnostic confirmation and drive neuronal loss; pSer129-aSyn sits in the core. The page records the JS aside that oligodendrocyte don't express SNCA so GCI α-syn likely arises from neuronal secretion, and the operator anchor that this motivates TAK-341 efficacy in MSA — preserved as written. Severely / moderately / mildly affected regions are listed on the canonical page along with Astrocyte inclusions (Radford 2014 #1417), the periventricular astrocyte P-αSyn note, and the Jellinger 2020 αSyn 140 / 122 / 126 isoform shift. The splice row on _184223 records (Brudek, 2016 #1425) αSyn 140 and 112 isoform levels are increased, whereas αSyn 126 is decreased, in SN, striatum & cbll; the 140 / 112 vs 140 / 122 spread between Brudek and Jellinger is preserved without reconciliation.
• Cell loss, demyelination, microgliosis, tau. (Refolo, 2018 #1419) no significant demyelination in mildly / moderately affected MSA brains; microglial activation accompanies GCI pathology in white matter with CD4 / CD8 T-cell infiltration. The Cristian MJFF PPMI 2023 CAS note records the hypothesised lack of tau pathology in MSA as a reason that emerging α-syn PET tracers’ tau off-target binding may not be an issue in MSA (md).
• Subtype clinical comparison. md carries the MSA-P / MSA-C / MSA-PC clinical-feature table (Stankovic 2019 #1649 records ~50% of MSA-P show additional cerebellar signs and ~75% of MSA-C develop parkinsonism during the disease course; Sakakibara 2000 #1448 anchors common autonomic dysfunction). The per-subtype urinary / orthostatic symptom percent figures (Figures 1 and 3) and prevalence comparison (HORC-MSA vs Kim 2011) are on the canonical page; cell values are not re-quoted here.
• Subtype pathology and MRI. md consolidates prevalence (Jellinger 2020 22/42 vs 20/42; Watanabe 2002 #1418 75/230 vs 155/230; HORC-MSA 29.9% / 58.2%; Kim 2011 #1391 55% / 17% / 28%), age-at-onset, time-to-disability stages, and MRI hyperintense putaminal rim / hot-cross-bun (HCB) / midline- hyperintensity (MH) / MCP-hyperintensity per Kim 2019 #1436; DATscan progression (김한준) faster progression than PD for MSA-P and barely changes for MSA-C; L-dopa response 42-57% vs 13-25% per Stankovic 2019 #1649. The Pathology schematic (Healthy / MSA-P-SND / MSA-C-OPCA / autonomic brainstem nuclei with Kuzdas-Wood 2014 #2131 caption) is preserved as evidence. Bottom-edge prevalence rows on _184230 show duplicated ± glyphs (62.3 ± 6.8.5) that resolve as 8.5 / 8.8 / 7.3 on _184233; preserve the divergence.

Cohort and Natural-History Studies

md anchors the cohort layer with NAMSA-SG (Gilman 2005 #2189 — 175 probable-MSA, 12 US sites, 6-monthly evaluations for 5 years; UMSARS / EMSA-SG minimal data set / COMPASS / SF-36 assessments; median illness duration 9.8 y; severe autonomic failure → 2.3 y shorter survival), EMSA-SG (Geser 2005 #2069 / Wenning 2013 #1077 — 412 patients, ≥141 longitudinal, 6-monthly for 2 y across 11 countries; UMSARS Part 1 / Part 2 progression in years 1 and 2), the TALISMAN observational study (Lundbeck-supported 140 early-stage MSA patients across EU and China with UMSARS Parts I and II as the 12-month primary endpoint and EU-cohort plasma NfL / imaging biomarkers; Lu AF82422 is currently the only anti-α-syn mAb under clinical development for MSA), and the P+A+MS clinic (Ndayisaba 2022 #2190 — Brigham and Women’s Harvard-affiliated parkinsonism-plus / ataxia / MSA clinic; 69-patient n-of-few recruitment with UMSARS / BARS / MoCA / NMSS / UPSIT / vMRI / FDG-PET / MIBG / PSG / skin biopsy / PBR06-TSPO panel; iPSC lines from MSA patients matched to postmortem brain). The 2022-06-11 Jaya operator note about scopes of work for Dr. Meissner and the French MSA Registry data access proposal is preserved on the canonical page; bullet leading glyph ☐ is a placeholder symbol preserved per Uncertain Spans. BioMUSE (Alterity’s natural-history study running alongside the ATH434 P2 RCT) is anchored from md.

Pipeline MSA — Disease-Modifying

The disease-modifying inventory spans the wide multi-row Pipeline MSA table on md and md, the KM-819 / IkT-148009 continuation block on md, and the Mészáros 2020 #1410 disease-modifying-targets table and Key Ongoing Trials Gantt panels.

• BIIB101 / ION464 (Biogen / Ionis) — SNCA ASO, P1 (Ionis framing P1/2 vs Biogen P1), DATscan-proven probable / possible MSA, IT q2-3w, NCT04165486, expected primary completion 2022-07. Preclinical (Cole 2021 #1450) PFF prevention / treatment / biodistribution rows and the Lim 2011 #1451 A53T-overexpression tetracycline-stop comparator are on the canonical page.
• ATH434 (Alterity, prana PBT434) — small-molecule labile-iron redistributor; new open-label P2 biomarker trial (start 2023-03, enrollment 15 (30), expected PCD Oct 2024; primary brain-MRI iron at week 52). Original P2 RCT in early MSA (≤3 y motor symptoms) with high / low / placebo on 60 patients; biomarkers span MRI iron QSM/R2*, neuromelanin, NfL, aggregating α-syn, phospho-α-syn, wearable movement sensors.
• ENT-01 (Enterin) — α-syn inhibitor displacing misfolded α-syn from enteric neurons; the page records a single prodromal MSA patient with ATP13A2 mutation use; received IND.
• Verdiperstat (BHV-3241 / AZD3241) — MPO inhibitor across two trial blocks: P2 NCT02388295 (AstraZeneca, 12 weeks, primary TSPO PET microglial activation in striatum) and P3 M-STAR NCT03952806 (Biohaven, 336 enrolled, 48 weeks, primary modified UMSARS). The 20210929) failed on both primary and key secondary efficacy measures readout is preserved on md. Asset-card description is partially right-edge clipped (trailing (total of 7 clinical ...) ellipsis preserved).
• AAV2-GDNF gene therapy (AskBio) — NCT04680065 P1, bilateral putaminal infusion, 2:1 randomised vs sham (blinded burr/twist hole comparator), up to 9 subjects. Endpoints TEAEs over 3 yeras (typo preserved), UMSARS, 123I FP-CIT DaT ratio, MSA-QoL.
• Lu AF82422 (Lundbeck) — P2 AMULET, anti-α-syn mAb NCT05104476, IV Q4W for 48-72 weeks, primary UMSARS Parts I and II. The Phase 2 → Phase 3 Bayesian-adaptive timeline diagram is preserved as evidence on the canonical page; secondary endpoint list (mUMSARS, SE-ADL, CGI-S, PGI-S, OGI-S, COMPASS, Part IV, Speech / Swallowing / Falls / Walking, Fall Diary, EQ-5D-5L, vMRI, DTI, NfL, Lu AF82422 PK / CSF) is on the canonical page. Lu AF82422 was granted Orphan Drug designation in the EU (April 2021) and Japan (date partial-clipped). 20240201 topline: primary endpoint did not meet statistical significance; positive trend with Lu AF82422 in slowing progression; OLE roll-over enables a delayed start analysis; Ph3 plans for 2025 with a 25% slowing of disease progression in 48 weeks benchmark (md).
• KM-819 (Kainos, FAScinate) — FAF1 inhibitor; first patient dosed in Korean Ph2 MSA 20230418; 36-week main study + 40-76 week OLE; primary putaminal [18F]FP-CIT change at week 36; UMSARS secondary (md, md). Asset row on _184226 is left-edge clipped (...819 / (...cinate), / ...tent inhibitor / ...AF1).
• IkT-148009 (Inhibikase, risvodetinib) — c-Abl kinase inhibitor; planned Ph2a '202' MSA study (6 months, UMSARS / QoL / orthostatic hypotension; biomarkers NfL, phospho-α-syn, MSA progression by MRI); MSA clinical hold lifted 2023-04-18 after the November 2022 vision-related-AE / 200 mg hold and the January 2023 partial PD-program lift (md).
• NMBI / emeramide (Irminix / EmeraMed) — lipid-soluble heavy-metal chelator + thiol-redox antioxidant; P2a NCT04184063 in PSP or MSA (16 patients, double-blind cross-over, 28 days); primary PSPRS change vs placebo (md).
• Mészáros 2020 #1410 disease-modifying-targets table — three target rows (α-syn aggregation: Affitope PD01A / PD03A vaccines P1, EGCG P3 NCT02008721; Neuroinflammation: Verdiperstat P3, CD20 rituximab P2 NCT04004819; Neuronal loss: BM-derived MSCs ×3 P1 NCTs, intranasal insulin P1, mTOR sirolimus P2 NCT02064166, antioxidant inosine 5’-monophosphate P2 NCT03589976) on md.
• Key Ongoing Trials for MSA Gantt (Takeda, March 2022) — Lu AF82422 Ph2 AMULET, ATH434 Ph2, BIIB101 Ph1/2 HORIZON, MODAG / Teva Anle-138b Ph1b (MSA development planned), Vaxxinity UB-312 Ph1 (MSA development planned), and Takeda / AstraZeneca TAK-341 / MEDI-1341 Ph1 HV / PD. The notes block records that ABBV-0805 (Anti-α-syn mAb) and PD01 / ACI-7104 (α-syn vaccine) also list MSA in their development plans (md). Slide footer 46 | GPLS Team. 1Q 2022 Quarterly and Key Events Report - Neurodegeneration | April 2022 | Confidential - for internal use only is preserved verbatim.

Pipeline MSA — Symptomatic

md reproduces the Mészáros 2020 #1410 symptomatic-targets table covering parkinsonism (MAO-B inhibitor safinamide, P2 NCT03753763), cerebellar ataxia (NMDA-receptor modulator Tllsh2910, P3 NCT03901638 — drug name preserved as written per Uncertain Spans), and orthostatic hypotension (midodrine P1, droxidopa P1 / P4, atomoxetine P2, ampreloxetine TD-9855 P2). NCT IDs and phase / reference columns are on the canonical page.

RBD as MSA Prodrome — Screening, Mechanism, Pathology / Imaging

md sits under the long inherited nav root Pipeline MSA > Disease-modifying > RBD screening question... > RBDQ-HQ (REM sleep...) > Mechanism > Pathology/Imaging and bundles the RBD-as-MSA-prodrome material into one page. Filed under sections/msa because of the nav-root, but content overlap with the prodromal RBD axis on biomarkers-outcomes is significant and is delegated there.

• Dx and screening tools. Clinical diagnosis per ICSD-3; definite diagnosis per video-PSG excessive EMG activity during REM sleep. RBDSQ (10-item, max 13; cut-off >5 per Stiasny-Kolster 2007 et al.); RBDSQ-J (Miyamoto 2009 #1435); RBDQ-HQ (Li 2010 #1434, 13-item, English-translated by authors); RBDQ-JP (Sasai 2012 #1433) — the RBDSQ paper- reproduction Table 1 is on the canonical page.
• Mechanism. Subcoeruleus / sub-laterodorsal nucleus, pedunculopontine nucleus, gigantocellular reticular nucleus — REM-active nuclei whose pharmacological activation induces REM motor atonia and whose lesions prevent it; cholinergic neurons involved in RBD.
• Pathology / Imaging. Boeve 2007 PMID 17157062 (RBD only, N=1, Lewy body disease but no significant neuronal loss or gliosis was present in the SN or LC — yellow-highlighted), Iranzo 2013 PMID 23562390 (RBD+PD ×2, RBD+DLB ×1, all three with brainstem / limbic Lewy pathology in subcoeruleus / PPN / gigantocellular nuclei), García-Lorenzo 2013 #1878 (rare brain- stem-lesion human RBD reports plus the Arnulf 2000 PD-with-RBD α-syn-in-LC/subcoeruleus case), and the García-Lorenzo 2013 imaging anchor — ↓ signal in neuromelanin-MRI in LC; the signal correlated with RBD severity (REM sleep without atonia) with r=~0.5. The page also lists Sleep. 2019 Jun 11;42(6). pii: zsz062 as a 내용 확인 필요 follow-up.
• Idiopathic RBD and animal model. Boeve 2007 N=1 and Iranzo 2013 N=4 idiopathic RBD rows. Animal-model aSyn PFF based mouse model records sublaterodorsal-tegmental-nucleus PFF injection → RBD-like behaviours and α-synopathy / neuron degeneration as the substrate; the citation cell (citation) is empty per Uncertain Spans.
• GBA → RBD penetrance / odds ratio. Penetrance row blank (No report?); odds ratio per Gan-Or 2015 PMID 26401515 (265 idiopathic RBD vs 189 in-house controls; OR 2.63 (95% CI 1.30–5.29, P = 0.0052) for all variants and 3.46 (1.40–8.56, P = 0.0045) for pathogenic variants). The pooled-control comparison cuts off mid-sentence and continues on 20240722_184434 (out of this section’s source set).

The page’s tail of an LRRK2 / GBA-NMC findings bullet block continued from 20240722_184427 (higher MDS-UPDRS Total / Part I-III, lower MoCA, higher SCOPA-AUT despite no DAT deficit; no difference in daytime sleepiness or RBD scores) is preserved on the canonical page only.

Mucolipidosis (ML) — TM in MSA Cross-Reference

md places a Mucolipidosis (ML) Type-IV reference table directly after the TM in MSA row of the MSA-subtype pathology table. The TM in MSA mini-table records two rows: a Behavior row with endpoint / biomarker JS planning prompts for MSA-P / MSA-C / MSA-PC, and an aSyn row anchoring (simoa-based) Antibody to MSA-specific aggregated aSyn to Juntendo (currently serum). The ML table covers Types I-IV (Type IV gangliosidosis.[3] / Berman / Ganglioside-neuraminidase deficiency, MCOLN1 mutations, Mucolipin1 endosomal LOF → lysosomal lipid accumulation and elevated lysosomal pH); per-type cell values, the Cao 2015 #1726 TRPML1-overexpression negative-correction note, the Schiffmann 2014 #1717 imaging study, and the Misko 2021 #1721 hypomyelinating- leukodystrophy / MLIV disease-progression curve sit on the canonical page. The standalone MLIV / TRPML1 / Niemann-Pick lysosomal narrative is owned by lysosome-autophagy.

Source Boundary / Delegation

This MSA topic is the primary owner for the 9 sources of msa. Material that lives elsewhere is linked, not re-narrated.

• α-Synuclein in MSA — CSF aSyn / brain aSyn / animal models. Tier 1 page 20240722_184156 (MSA > aSyn in MSA > CSF aSyn in MSA) is filed under sections/gba-pd-asyn and is owned by alpha-synuclein. That page bundles Booth 2015 #1745 MRI/MRS reviews, the (PLP)- / (CNP)-hα-syn / viral-oligodendrocyte / Cre-loxP / MBP-aSyn (Ubhi 2010) animal- models-of-MSA table, the Schweighauser 2020 #2060 / Peng 2018 #2062 / Prusiner 2015 #2063 brain-aSyn filament biology, and the Ateno 2012 / Mavroudis 2020 / ga 2018 / ulds 2012 CSF aSyn studies. This page does not re-narrate that material.
• NfL and RBD prodromal stratification. The corpus’s whole-NfL axis (PD vs MSA cohort comparisons via Nocker 2012, Poewe 2015, Wild 2009, Chelban 2022 #310, Mollenhauer DeNoPa) and the prodromal RBD axis (GBA → RBD penetrance, RBD → PD/MSA/PDD-DLB conversion, GBA pathway in RBD figure, PSYCHIATRIC OUTCOMES IN PD slide) are owned by biomarkers-outcomes. This MSA topic owns only the MSA-specific NfL longitudinal table on 20240722_184216 and the RBD-screening / mechanism / pathology / animal-model / GBA → RBD-OR page on 20240722_184430 because both pages are filed under sections/msa.
• Mucolipidosis (ML) / TRPML1 lysosomal biology. The MSA topic records only the TM in MSA > Mucolipidosis (ML) cross-reference cell on 20240722_184233; the broader lysosomal narrative sits under lysosome-autophagy.
• Anti-α-syn programs. alpha-synuclein and therapeutic-programs own per-program narrative for TAK-341 / MEDI1341, SNCA ASO (WAVE), SNCA BTV (HDO), the aSyn programs umbrella, and the Pipeline-of- PD aSyn-Antibody / Vaccine / Small-molecules rows. This MSA topic surfaces only the MSA-specific pipeline rows (Lu AF82422 P2 AMULET, BIIB101 / ION464 P1/2 HORIZON, Anle-138b Ph1b, UB-312 Ph1, TAK-341 / MEDI-1341 Ph1, Affitope PD01A / PD03A vaccines, ABBV-0805, PD01 / ACI-7104).
• PET / Imaging modalities. pet-imaging owns the broader imaging / tracer-development axis. This MSA topic surfaces a modality only when it appears as an MSA-trial-specific endpoint (Verdiperstat P2 TSPO PET primary; KM-819 putaminal [18F]FP-CIT primary; ATH434 brain-MRI iron primary; AAV2-GDNF 123I FP-CIT DaT secondary; García-Lorenzo 2013 NEUROmelanin-MRI in RBD imaging).

Source Table

A single chronological table covering every source assigned to this topic. Numeric uncertain spans and embedded images are copied verbatim from each source-note’s quality_metrics.

stem	nav path / heading	source note	canonical	uncertain spans	embedded images
20240722_184206	MSA	note	md	1	0
20240722_184210	MSA > Dx of MSA > Imaging	note	md	3	0
20240722_184216	MSA > Outcome Measures > Unified MSA Rating Scale (UMSARS)	note	md	5	0
20240722_184219	MSA > Outcome Measures > Pathology	note	md	2	0
20240722_184223	MSA > Pipeline MSA > Disease-modifying	note	md	2	0
20240722_184226	MSA > Pipeline MSA > Disease-modifying	note	md	4	0
20240722_184230	Pipeline MSA > Subtype	note	md	5	0
20240722_184233	MSA > Pathology > TM in MSA > Mucolipidosis (ML)	note	md	4	0
20240722_184430	Pipeline MSA > Disease-modifying > RBD screening question… > RBDQ-HQ (REM sleep…) > Mechanism > Pathology/Imaging	note	md	3	0

Totals across these 9 sources: uncertain_span_count = 29, embedded_image_count = 0. Review surface area, not resolutions.

Uncertainties Carried Forward

Review-priority hot spots preserved from each source-page Uncertain Spans table. Re-check the canonical page before any downstream extraction; do not paraphrase the uncertain content.

• 20240722_184216 (5) — top-of-page continuation header from _184213; Bridel forest-plot fold change 3.63 (2.77-4.75); London-cohort scatter inset r=0.845, p=0.001; Hansson n 5 278 / n 5 117 glyph; Constantinesu vs Constantinescu surname.
• 20240722_184230 (5) — Tllsh2910 symptomatic-table drug name; ABBV-0805 right-margin clipping (Initiation of Ph2 study expected in 2022 vs likely H2 2022); duplicated decimals in bottom-edge prevalence row; status-bar tan in the other types; the Subtype clinical row arrow / ie glyph.
• 20240722_184226 (4) — Verdiperstat P2 right-notes column bracketed reconstructions; Lu AF82422 right-column received Orphan drug designation in Japan; partial visibility; KM-819 left-edge clipping; AAV2-GDNF endpoint Primary: TEAEs over 3 yeras typo preserved.
• 20240722_184233 (4) — bottom-edge ± glyph reads as 6 on _184230 and resolves on _184233; TRPML1 / ML1-/- / 'ML4 construct labels mixed in Cao 2015 #1726 bullet; Mucolipidosis-table Subtype and TM in MSA rows clipped beneath the Stage progression figure (continues on _184247); Type II SYNONYM I-Cell Disease two-line layout.
• 20240722_184210 (3) — In-vitro-systems Authors column left-edge clipping for four rows; imaging footnote glyph 3) may be footnote 33; Possible MSA-C prose form ends mid-sentence.
• 20240722_184430 (3) — Pathology / Imaging table first-row label appears blank (continuation of merged cell on _184427?); Stiany-Kolster vs Stiasny-Kolster spelling; animal-model (citation) empty placeholder.
• 20240722_184223 (2) — ENT-01 single-prodromal-MSA-patient cell with ATP13A2 mutation; Verdiperstat asset card right-column (total of 7 clinical ...) ellipsis truncation.
• 20240722_184219 (2) — ICLEMSA SRM 전반적으로 cerebellar sign 들이네 confidence ~95%; MSA cerebellar ataxia dominant subtype trailing punctuation cut at line break.
• 20240722_184206 (1) — TALISMAN bullet leading symbol ☐ placeholder.
• Cross-page Verdiperstat P2 vs P3 readout. Verdiperstat appears as a Mészáros 2020 #1410 row, a P2 NCT02388295 asset card on _184223, and a P3 NCT03952806 M-STAR card on _184226; the 20210929) failed on both primary and key secondary efficacy measures note on _184223 is the P3 readout. Read in reading order rather than reconciling.
• Bridge to 20240722_184156 (alpha-synuclein topic). The MSA aSyn axis (MSA > aSyn in MSA > CSF aSyn in MSA) is owned by alpha-synuclein; the JS summary CSF aSyn 은 MSA 에서 정상과 차이가 없고, exosome aSyn 은 결과가 inconsistent 하니, 유용없으나, tak-341 의 response 로서 감소를 보는 의미는 있겠다. lives there. Cross-check before reading this page’s pathology splice / Inclusions text against CSF / brain aSyn quantification claims.

Related Pages

• Sections: msa (9), gba-pd-asyn (198), biomarkers-outcomes (27), lysosome-autophagy (5), pet-imaging (16).
• Topics: alpha-synuclein (Tier 1 owner of MSA > aSyn in MSA > CSF aSyn in MSA), biomarkers-outcomes (NfL across PD / MSA cohorts and RBD prodromal stratification), therapeutic-programs (program routing for TAK-341 / SNCA ASO / SNCA BTV / aSyn programs).
• Maps: alpha-synuclein-source-boundary (records topics/msa as the primary owner of the 9 MSA Tier 2 sources), document-outline, source-catalog, nav-path-index.
• Per-nav-root indexes: msa (8 rows; includes 20240722_184156 owned by alpha-synuclein), pipeline-msa (2 rows), rbdq-ho-rem-sleep (RBD screening sibling).