LRRK2-targeting antisense oligonucleotide in Parkinson's disease: a phase 1 randomized controlled trial - PubMed
4 hours ago
- #LRRK2
- #Parkinson's disease
- #antisense oligonucleotide
- LRRK2 variants are the most common genetic cause of Parkinson's disease (PD).
- BIIB094 (ION859), an antisense oligonucleotide, targets LRRK2 mRNA for degradation.
- REASON was a phase 1 study assessing safety, tolerability, pharmacokinetics, and pharmacodynamics of intrathecal BIIB094 in PD patients.
- Part A involved 40 participants receiving single doses of BIIB094 (10-150 mg) or placebo.
- Part B involved 42 participants receiving four doses of BIIB094 (40-120 mg) or placebo every 4 weeks.
- Adverse events were mostly mild to moderate, with no serious adverse events related to BIIB094.
- BIIB094 reduced CSF LRRK2 and phosphorylated Rab10 levels by up to 59% and 50%, respectively.
- Reductions in CSF lysosomal protein levels suggest a potential mechanism for LRRK2 therapeutics in PD.
- The study indicates BIIB094 may modify PD-associated neuropathology.