Chinese researchers have reported encouraging early results for a domestically developed experimental therapy targeting a genetic form of amyotrophic lateral sclerosis, or ALS. In a six-patient trial published this month in Nature Medicine, the drug was generally well tolerated and reduced key disease-related biomarkers.

Called RAG-17, the therapy uses small interfering RNA, or siRNA, to suppress SOD1, a gene whose mutations can cause ALS. By reducing production of the harmful protein associated with the mutation, the drug is designed to target a biological driver of the disease.

ALS is a progressive neurodegenerative disease that destroys the nerve cells controlling voluntary movement, gradually impairing a patient’s ability to move, speak, swallow, and breathe. The disease gained wider public attention through campaigns such as the Ice Bucket Challenge, but it remains incurable.

China has an estimated 60,000 to 100,000 people living with ALS, with about 23,000 new cases diagnosed each year. Around 2% of patients carry SOD1 mutations, the only genetic form of ALS with an approved targeted treatment. Tofersen, the first approved therapy targeting SOD1-related ALS, received U.S. approval in April 2023 and was approved in China in September 2024.

RAG-17 was jointly developed by a team led by Wang Yilong at Beijing Tiantan Hospital and researchers led by Li Longcheng at biotech company Ractigen Therapeutics.

In the trial, six patients with SOD1-related ALS received repeated injections of the drug into the fluid surrounding the spinal cord over several months. Researchers reported no serious adverse events. Two participants experienced mild muscle tremors that later resolved.

The treatment produced substantial reductions in two disease-related biomarkers. 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 changes indicate that RAG-17 reached its intended target.

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

The Chinese research team said a larger clinical trial of RAG-17 is now underway.

Editor: Apurva.

(Header image: Shijue Focus/VCG)