Starting with RNA Repair: ALS Candidate TRCN-1023 Enters Human Trials for the First Time

Treatment options for amyotrophic lateral sclerosis (ALS) are limited, and most patients do not have a single, clearly actionable disease-causing mutation. Trace Neuroscience is now bringing another approach into human studies: rather than rewriting DNA, it is using the antisense oligonucleotide TRCN-1023 to modify RNA processing in an attempt to restore the function of the UNC13A protein impaired in the disease.

TRCN-1023 binds directly to UNC13A messenger RNA, guiding cells to produce functional protein. UNC13A is involved in signal transmission between neurons and between nerves and muscles; the developer and its academic partners estimate that loss of its function is implicated in approximately 97% of ALS cases. The drug must be delivered by intrathecal injection into the cerebrospinal fluid surrounding the spinal cord to reach the central nervous system, which is primarily affected by the disease.

The clinical program is proceeding along two parallel tracks. The randomized, double-blind, placebo-controlled Phase 1/2 FUNCTION ALS trial has been authorized in the UK and the Netherlands and is expected to enroll approximately 30 patients across Europe and North America. UK trial sites include Sheffield Teaching Hospitals and University College London Hospitals, with Pamela Shaw, professor of neurology at the University of Sheffield, serving as chief investigator. The study registration number is NCT07674667.

A second study, LAUNCH ALS, has begun at Beijing Tiantan Hospital under the leadership of Wang Yilong and is being conducted through a collaboration between Trace and Tiantan Biopharmaceutical. The first patients received treatment in June 2026, and approximately 25 participants are expected to be enrolled in total. The two studies use similar eligibility criteria, allowing early human data to be accumulated simultaneously across different regions.

In FUNCTION ALS, participants will receive TRCN-1023 or placebo and be followed for 24 weeks. The primary assessments are safety, tolerability, pharmacokinetics, and pharmacodynamic activity. The study will also analyze biomarkers and use digital tools to measure changes in movement and speech. Registration data indicate that participants must be 18 to 75 years old, have experienced symptoms for no more than 24 months, and have a slow vital capacity of at least 60% of the predicted value. People with confirmed SOD1 or FUS mutations will not be included.

However, the two studies, with approximately 55 participants in total, are limited in scale. Their core task remains to determine the risks of administration, the drug’s behavior in the body, and its effects on the target—not to prove that it can slow disability or extend survival. Even if biomarkers show that UNC13A function has been restored, larger and longer controlled trials will still be needed to determine whether this molecular change translates into clinical benefits that patients can actually perceive.