Trace Neuroscience announced on Mar. 25 that it is developing a new approach to treat amyotrophic lateral sclerosis (ALS) by targeting the UNC13A protein, aiming to improve outcomes for patients with the neurodegenerative disease.
The effort comes as people diagnosed with ALS have seen little change in available treatments over recent years. Trace’s technology is based on research from University College London, where neurologist Pietro Fratta and his team found that individuals with ALS have low levels of the UNC13A protein, which plays a role in neuronal communication. A similar discovery was made by scientists at Stanford, leading both teams to publish their findings simultaneously in 2022 and eventually collaborate to form Trace Neuroscience.
Trace’s lead clinical candidate, TRCN-1023, is an antisense oligonucleotide designed to restore UNC13A function. The drug will be delivered intrathecally into the cerebral spinal fluid. Chief Executive Officer Eric Green said Trace will use biomarkers—specifically neurofilament light chain—to track treatment efficacy in studies of its UNC13A-targeting therapies. This biomarker approach follows lessons learned from Biogen’s tofersen (Qalsody), which was approved in 2023 for patients with a SOD1 gene mutation linked to familial ALS.
“We very much see the work that was done in developing tofersen as setting the stage for what we plan to do,” Green said.
Green also credited advances in biomarker understanding and persistent unmet need as driving renewed investment and interest from large pharmaceutical companies in neurodegenerative disease research. He noted that ALS progresses rapidly enough that potential clinical benefits or setbacks can be observed sooner than with many other diseases: “Six months in an untreated person with ALS, you expect to see considerable changes...and so that gives us an opportunity to see relatively quickly if we’re seeing benefit with our treatment,” Green said.
Looking ahead, Trace plans over the next year to move TRCN-1023 into clinical trials involving people living with ALS rather than healthy volunteers. Green added that growing evidence suggests targeting UNC13A could also be relevant for other neurodegenerative conditions such as frontotemporal dementia or Alzheimer’s disease: “ALS is where we’re starting, but [we] see a number of opportunities to expand quickly into these other disease areas,” he said.
