Trace Neuroscience is a biotechnology company developing precision genetic medicines for neurodegenerative diseases, with a primary focus on Amyotrophic Lateral Sclerosis (ALS). The company's strategy is centered on a key pathological hallmark present in approximately 97% of ALS patients: the mislocalization of the TDP-43 protein, which leads to the improper splicing of UNC13A mRNA. This results in a functional deficiency of the UNC13A protein, a crucial component for enabling communication at the synapses between nerve and muscle cells.
Trace's lead program is an antisense oligonucleotide (ASO) designed to specifically correct this aberrant splicing, restore the production of functional UNC13A, and thereby rescue synaptic function to slow disease progression. By targeting this common underlying mechanism, Trace aims to expand the promise of genetic medicine from the 2% of ALS patients with targetable SOD1 mutations to the vast majority of the patient population. The company's approach has potential applications in other neurodegenerative conditions linked to UNC13A deficiency, such as frontotemporal dementia (FTD).
Trace Neuroscience's Mission to Tackle ALS
The Core Problem in 97% of ALS Patients: Trace Neuroscience is targeting a widespread issue in ALS where a protein, TDP-43, malfunctions and moves out of the cell's nucleus. This disruption causes the genetic instructions for a vital protein, UNC13A, to be read incorrectly, a process known as mis-splicing.
The Critical Role of UNC13A: The UNC13A protein is essential for the proper function of synapses, the communication points between nerve and muscle cells. It primes vesicles for neurotransmitter release. A lack of functional UNC13A leads to a breakdown in this communication, resulting in the progressive muscle weakness and paralysis seen in ALS.
Trace's Targeted Solution: The company is developing an antisense oligonucleotide (ASO), a type of genetic medicine. This ASO is engineered to bind directly to the faulty UNC13A messenger RNA (mRNA) and correct the splicing error, allowing cells to produce the functional protein once again.
Goal: A Breakthrough for the Majority: While existing genetic therapies like Qalsody only address about 2% of the ALS population (those with SOD1 mutations), Trace's approach targets the TDP-43 pathology present in nearly all other patients. Their mission is to expand the reach of effective genomic medicine to the other 98% of people with ALS.
Company Leadership and Origins: The company was co-founded by CEO Eric Green, M.D., Ph.D., an experienced drug developer, and the academic scientists who made the breakthrough discoveries linking TDP-43 pathology to UNC13A deficiency, including Aaron Gitler of Stanford and Pietro Fratta of University College London.
Clinical and Future Plans: Trace is advancing its lead ASO candidate, TRCN-1023, and is on track to begin human clinical trials in early 2026. The company is also researching biomarkers to identify patients most likely to benefit and believes the UNC13A restoration approach could also be applied to other neurodegenerative diseases like frontotemporal dementia (FTD) and Alzheimer's.
Industry Recognition: Highlighting its innovative approach and potential impact, Trace Neuroscience was named one of Fierce Biotech's "Fierce 15" companies of 2025.