Chinese Gene-Silencing Drug Reduces ALS Biomarkers in Small Trial

Chinese researchers have reported early results from a six-patient trial of RAG-17, an experimental gene-silencing therapy for a genetic form of amyotrophic lateral sclerosis (ALS). The study was published this month in Nature Medicine.

RAG-17 uses small interfering RNA (siRNA) to suppress the SOD1 gene, whose mutations account for roughly 2% of ALS cases and drive production of a toxic protein that damages motor neurons. The drug was jointly developed by a team led by Wang Yilong at Beijing Tiantan Hospital and researchers led by Li Longcheng at Ractigen Therapeutics.

In the trial, six patients with SOD1-related ALS received repeated intrathecal injections of the drug over several months. No serious adverse events were recorded; two participants experienced mild muscle tremors that later resolved.

Biomarker analysis showed SOD1 protein levels in cerebrospinal fluid fell by more than half, while plasma levels of neurofilament light chain, a marker of nerve-cell damage, also declined. The researchers said these changes indicate the therapy reached its intended target in the central nervous system.

Preclinical studies in rodent models of SOD1-related ALS found that RAG-17 delayed disease progression, preserved motor function, and extended survival. Tests in macaques demonstrated sustained suppression of the SOD1 gene in the central nervous system.

ALS is a progressive neurodegenerative disease that gradually impairs movement, speech, swallowing, and breathing. China has an estimated 60,000 to 100,000 people living with ALS, with about 23,000 new cases diagnosed each year.

The only approved targeted treatment for SOD1-related ALS, tofersen, received U.S. approval in April 2023 and Chinese approval in September 2024. A larger clinical trial of RAG-17 is now underway.

The current findings are limited by the very small sample size and lack of a control group; the researchers emphasize that further studies are needed to assess clinical benefit.