Variants in the LRRK2 gene represent the most common known genetic cause of Parkinson's disease, and scientists have long suspected that reducing the protein it produces could slow or alter the course of the illness. Now, results from the first human trial of a drug designed to do exactly that suggest the approach is both safe and biologically active in the brain.
The phase 1 trial, called REASON, tested an antisense oligonucleotide known as BIIB094, developed by Biogen, which works by targeting LRRK2 messenger RNA for degradation. The drug was delivered directly into the spinal fluid of 82 participants with Parkinson's disease across two parts of the study. Results published in Nature Medicine showed that BIIB094 reduced cerebrospinal fluid levels of the LRRK2 protein by up to 59 percent and a related marker called phosphorylated Rab10 by up to 50 percent. Crucially, those reductions occurred regardless of whether participants carried an LRRK2 genetic variant.
Safety was a key focus of this early-stage trial. Adverse events were mostly mild to moderate, with no serious side effects attributed to the drug in either phase. In part A, 64.5 percent of participants who received BIIB094 reported adverse events, compared with 84.8 percent in the multi-dose part B — figures that researchers noted were consistent with what is typically seen in trials involving intrathecal injections.
Beyond the protein reductions, the researchers observed something that could prove equally significant. Levels of lysosomal proteins in cerebrospinal fluid also declined alongside LRRK2, suggesting a possible mechanism through which the drug might influence the underlying biology of Parkinson's disease. Lysosomal dysfunction has been implicated in the buildup of toxic proteins in the brains of Parkinson's patients, making this finding a potentially important clue for future research.
The trial was not designed to measure whether BIIB094 actually slows disease progression — that question will require larger, longer studies. But the demonstration that an antisense oligonucleotide can safely reach the brain and meaningfully suppress its genetic target is an encouraging milestone. It adds to a growing body of work exploring precision approaches to neurodegenerative diseases, moving beyond symptom management toward treatments that address root causes.
