PR001
PR001 is the pilot’s GBA gene-therapy program. The source pages cover in vitro work, CBE-treated mice, 4L/PS-NA genetic mice, A53T + CBE alpha-synuclein mice, NHP ICM biodistribution, GCase expression, safety margin, dose selection, and the first visible clinical-trial row. Sources: 20240722_181800 , 20240722_181805 , 20240722_181809 .
Evidence Package
evidence area source-captured detail source In vitro Vehicle, low-dose, and high-dose PR001 groups with vg/cell values; figure retained in source. 20240722_181800 CBE mice, short-term ICV PR001 low/medium/high dose in CBE-treated mice; highest dose improved motor function; GCase activity correlated positively with rotarod and negatively with brain glycolipids. 20240722_181800 CBE mice, longer-term Vector genomes detected in brain/spinal cord 5 weeks after administration; highest dose increased GCase in brain/spinal cord; 6-month note says GCase remained increased and lipid accumulation reduced. 20240722_181805 4L/PS-NA genetic model Single-dose ICV PR001 in 4L/PS-NA mice; source distinguishes cortex GBA activity, cerebellum GlcCer/GlcSph, and cortex alpha-synuclein. 20240722_181805 Alpha-synuclein Source states PR001 halved insoluble alpha-synuclein in 4L/PS-NA and A53T + CBE contexts; figure evidence is retained. 20240722_181805 , 20240722_181809 NHP ICM biodistribution Heatmap gives vector genomes per ug DNA tissue across hippocampus, periventricular tissue, putamen, ventral midbrain, and spinal cord regions. 20240722_181809 NHP GCase expression SimpleWestern-based GCase levels in cortex/hippocampus/midbrain; low and high dose showed elevated GCase 6 months after ICM injection; source table approximates around 120% of control. 20240722_181809 Dose selection Mouse efficacy identified predicted brain biodistribution; NHP toxicology identified an ICM dose with comparable brain exposure; NHP dose was scaled to humans by brain weight. 20240722_181809 Clinical trial entry PROPEL NCT04127578 appears as P1/1a in GBA-PD, H&Y 3-4 off, heterozygous, n=16, randomized open-label sham-procedure-controlled ascending-dose FIH study; bottom row is clipped. 20240722_181809
Key Source Interpretations
interpretation source In the CBE mouse source table, GBA activity had to rise well above normal control before GlcCer/GlcSph approached normalization. 20240722_181805 In the 4L/PS-NA summary table, source notes alpha-synuclein changed even without GlcCer/GlcSph change, suggesting GBA activity may affect alpha-synuclein through a route not fully captured by lipid normalization. 20240722_181805 The NHP page explicitly says Prevail did not publish cellular transduction data, but did report vector genome copy / brain exposure and widespread GCase expression. 20240722_181809
source figure group 20240722_181800 PR001 in vitro bars; CBE biomarker plots. 20240722_181805 Prevail CBE treatment; PR001 single-dose model diagram; biodistribution/GCase; lipid accumulation; insoluble alpha-synuclein partial plot. 20240722_181809 4L/PS-NA mouse figure; A53T CBE ASGCT figure; NHP biodistribution; NHP GCase barplot.
Uncertainties Carried From Source
issue source Multiple vector-genome dose bases appear across pages (vg/cell, vg, vg/g brain, vg/brain); preserve exact wording. 20240722_181800 , 20240722_181805 , 20240722_181809 Several PR001 plot captions and axis values are kept as images because exact values are too small. 20240722_181800 , 20240722_181805 201906 US SECURI AND COMMISION is visibly misspelled/truncated in source and not normalized here.20240722_181805 4L/PS-NA + 1.3E+?? vg PR001 remains unresolved in the figure label.20240722_181809 NHP heatmap values are small scientific notation values and should be checked before downstream structured extraction. 20240722_181809 PROPEL clinical-trial row is clipped and should be expanded from the next source photo. 20240722_181809