Trace Neuroscience has emerged with $101 million in Series A financing, spearheaded by Third Rock Ventures, to advance genomic therapies aimed at restoring UNC13A protein function in neurodegenerative diseases. The company's primary focus is on developing an antisense oligonucleotide (ASO) to treat amyotrophic lateral sclerosis (ALS), including the sporadic form affecting approximately 90% of ALS patients.
Targeting UNC13A for ALS Treatment
Trace Neuroscience's strategy centers on UNC13A, a protein crucial for nerve-muscle cell communication. Dysfunction of the TDP-43 protein, which regulates UNC13A, is implicated in nearly all ALS cases. When TDP-43 malfunctions, UNC13A mRNA splicing is disrupted, leading to inadequate UNC13A production and impaired neuronal signaling.
The company's ASO candidate is designed to bind directly to UNC13A mRNA, regulating its processing to ensure proper splicing. This targeted intervention aims to correct synaptic dysfunction and preserve neuronal signaling, potentially slowing disease progression and improving outcomes for ALS patients.
Scientific Rationale and Expert Perspectives
"Genomic-based therapies have begun to transform the lives of people living with ALS. But so far, they have only been effective for those rare forms of the disease caused by SOD1 or FUS mutations, which account for only 3% of all ALS cases," said Trace co-founder Aaron Gitler, PhD, professor of genetics at Stanford University. He emphasized the need for new treatments grounded in human genetics for the remaining people, including those with sporadic disease.
Eric Green, MD, PhD, co-founder and CEO of Trace, added, "UNC13A is a highly compelling genetic target directly linked to ALS disease progression and survival... we believe the time is right to apply this approach to ALS." He envisions UNC13A restoration improving outcomes across a range of neurodegenerative diseases.
Pietro Fratta, MD, PhD, professor of cellular and molecular neuroscience at the University College London and Francis Crick Institute, highlighted the significance of re-establishing synaptic function, which is lost in ALS. "UNC13A is critical for neurons to communicate amongst each other and with muscles through synaptic function, which is lost in ALS. Being able to re-establish this is groundbreaking."
Implications for ALS Treatment Landscape
ALS affects approximately 30,000 people in the U.S., with a significant unmet need for effective treatments, particularly for the sporadic form of the disease. Current genomic therapies are primarily effective for rare, mutation-driven ALS cases, leaving a large portion of patients without targeted options. Trace Neuroscience's approach addresses this gap by targeting UNC13A, a factor relevant to nearly all ALS patients, offering a potential therapeutic avenue for a broader patient population.
