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Abstract LRRK2 (encoding leucine-rich repeat kinase 2) variants are the most common genetic cause of Parkinson’s disease (PD). Lowering LRRK2 levels and/or inhibiting LRRK2 activity may modify PD-associated neuropathology. BIIB094 (ION859), an antisense oligonucleotide, targets LRRK2 mRNA for degradation. REASON was a first-in-human randomized phase 1 study investigating the safety, tolerability, pharmacokinetics and pharmacodynamics of intrathecal BIIB094 in patients with PD.
Results Our CSF analysis included longitudinal CSF samples from 70 subjects enrolled in VALOR Part C7 with available material for all collection time points from baseline through week 16 (five time points). In line with the trial randomization (2:1 tofersen:placebo), our cohort consisted of 47 subjects in the tofersen treatment group and 23 subjects in the placebo arm (Figure 1A), which allowed us to randomly distribute subjects in a 2:1 ratio across 16-plex tandem mass tagged (TMT) sample sets.
Abstract Predicting not just if, but also when, cognitively unimpaired individuals are likely to develop onset of Alzheimerʼs disease (AD) symptoms would be useful to clinical trials and, eventually, clinical practice. Although clock models based on amyloid and tau positron emission tomography have shown promise in predicting the onset of AD symptoms, a model based on plasma biomarkers would be more accessible.
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