RAG-17 shows promise in SOD1-ALS trial, reducing damage markers

RAG-17, an experimental treatment Ractigen Therapeutics is developing for people with amyotrophic lateral sclerosis (ALS) who carry a SOD1 mutation (SOD1-ALS), was well tolerated at multiple doses and led to profound changes in disease biomarkers, preliminary trial data showed.

The data cover the first part of an ongoing Phase 1/2 clinical trial (NCT06556394), in which participants received a single injection of RAG-17 at doses ranging from 30-180 mg, or a placebo.

Results showed that the highest dose reduced neurofilament light chain (NfL) levels, a marker of nerve cell damage, by 81.2% and led to minimal changes in disease severity over about five months.

The findings were shared at the American Academy of Neurology (AAN) 2026 annual meeting, held April 18-22 in Chicago and online, in a poster titled, “Phase I Study of RAG-17, an siRNA Therapy Targeting SOD1, in Patients with SOD1-ALS: Preliminary Safety, Biomarker and Efficacy Data.”

Phase 2 of the trial is now underway to assess the safety and effectiveness of RAG-17 when given repeatedly, at ascending doses. Two dosing groups have been enrolled so far.

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‘Unprecedented’ results

“The data presented at AAN this year represents a major milestone for Ractigen and, more importantly, for patients living with SOD1-ALS,” Long-Cheng Li, MD, Ractigen’s founder and CEO, said in a company press release. “Achieving an 81% reduction in plasma NfL—a critical marker of [nerve cell] damage—alongside a highly favorable safety profile from a single administration is unprecedented.”

Up to 20% of familial ALS cases and about 2% of sporadic ALS cases are associated with mutations in the SOD1 gene. These mutations result in the production of an abnormal SOD1 protein that is prone to forming toxic clumps, contributing to nerve cell damage.

RAG-17 is a small interfering RNA (siRNA) designed to reduce levels of abnormal SOD1. It works by binding to SOD1′s messenger RNA, the intermediate molecule that serves as a template for protein production, and targeting it for destruction.

The therapy is administered via injection into the spinal canal (intrathecal injection).

The Phase 1/2 clinical trial is testing RAG-17 in about 32 adults with SOD1-ALS. Part 1 involved 20 participants who received a single injection of RAG-17 at five increasing doses — 30 mg, 90 mg, 120 mg, 150 mg, and 180 mg — or a placebo, in addition to standard ALS therapies.

Researchers demonstrated that RAG-17 was well tolerated at all tested doses, with no serious side effects or severe treatment-emergent side effects. Three treatment-emergent adverse events were reported, all of them mild.

Biomarker data also showed that RAG-17 binds to the intended target, with patients exhibiting rapid and durable reductions in SOD1 protein in cerebrospinal fluid (CSF, the fluid that surrounds the brain and spinal cord). In patients treated with the 150 mg dose, SOD1 was reduced by up to 58.1% after three months, and the effect was sustained as long as seven months after the injection.

RAG-17 also led to “progressive and significant” reductions in NfL blood levels, with the 180 mg group seeing an 81.2% drop in these levels over five months. The three patients in the group with at least one functional assessment — using the ALS Functional Rating Score-Revised (ALSFRS-R) — after dosing showed no functional decline after three months, and minimal decline after five months.

“What we observed in this Phase I study—a substantial and durable reduction in CSF SOD1 protein after a single dose, accompanied by a profound decrease in plasma NfL and early stabilization of functional scores in the highest dose group—gives us strong reason for optimism,” said Zhi-Ying Wu, MD, PhD, professor at Zhejiang University and a principal investigator in the trial. “These data clearly suggest that RAG-17 is engaging its target in a highly meaningful way, and we look forward to generating further evidence in the ongoing Phase II study.”