- University of Sheffield researchers are taking part in a trial of a pioneering experimental drug for motor neuron disease (MND)
- The novel investigational drug, TRCN-1023, is designed to target one of the most important genetic drivers of MND/ALS, the UNC13A protein
- The new programme combines two early-stage studies: FUNCTION ALS - a Phase 1/2 clinical trial authorised to begin shortly in the UK, with plans to expand to other countries in 2026 and LAUNCH ALS - an investigator-led trial already underway in China, where the first patients have recently been dosed
A pioneering experimental treatment for motor neuron disease (MND) is set to be trialled in humans as part of a new international clinical programme.
Developed by UCL spinout Trace Neuroscience, University of Sheffield researchers are taking part in an investigational drug trial, designed to target one of the most important genetic drivers of MND, the UNC13A protein.
Trace Neuroscience was co-founded by Professor Pietro Fratta of UCL Queen Square Institute of Neurology and has opened two trials for the drug TRCN-1023, a potential new treatment for MND, also known as amyotrophic lateral sclerosis (ALS) - the disease's most common subtype.
Its development builds on previous research which established the biological importance of the UNC13A protein in causing MND/ALS, and is now considered one of the most promising drug targets for the disease.
The trials are designed to accelerate development and build early global clinical evidence for TRCN-1023.
MND/ALS is a devastating and ultimately fatal disease, that causes progressive muscle weakness due to the degeneration of motor neurons in the brain and spinal cord. As the disease advances, patients gradually lose the ability to move, speak, swallow and breathe.
It is estimated to affect one in 300 people in their lifetime, and there are currently no disease-modifying drugs available to treat the condition.
Loss of UNC13A function is believed to contribute to disease progression in around 97 per cent of people with MND/ALS, making it one of the most relevant targets.
Dame Pamela Shaw, Professor of Neurology at the University of Sheffield and Chief Investigator for FUNCTION ALS, said: "UNC13A is among the most promising targets in ALS research today, with a strong grounding in human genetics and disease biology.
"Restoring its function could benefit the vast majority of patients."
TRCN-1023 is a type of medicine known as an antisense oligonucleotide (ASO) and has been designed to restore the normal function of the UNC13A protein, which plays a critical role in communication between nerves and muscles.
The drug works as the level of RNA - the intermediary between genes and proteins.
ASOs are short, synthetic strands of nucleic acid. They bind to RNA inside cells to influence how specific proteins are made. In this case, TRCN-1023 is designed to correct the processing of UNC13A RNA, enabling the body to produce a functional version of the protein.
TRCN-1023 is administered via an intrathecal injection - a procedure that delivers the drug directly into the fluid surrounding the spinal cord.
This approach is commonly used for ASO therapies because it allows the treatment to reach the central nervous system, where MND/ALS causes damage.
Professor Pietro Fratta, MRC Senior Clinical Fellow and MNDA Lady Edith Wolfson fellow at the UCL Queen Square Institute of Neurology, said: "UNC13A is critical for neurons to communicate amongst each other and with muscles and is lost in nearly all MND/ALS cases.
"Seeing this discovery translated into a clinical trial is a major milestone. It brings us a step closer to a therapy that could make a meaningful difference for the vast majority of people living with MND/ALS."
Eric Green, co-founder and CEO of Trace Neuroscience, said: "Our team helped establish UNC13A as one of the most compelling genetically validated targets in ALS, and we built Trace Neuroscience to translate that biology into a medicine.
"We're now excited to advance TRCN-1023 into the clinic through a global strategy designed to generate robust data with the urgency this disease demands."
The FUNCTION ALS study will enrol around 30 participants across sites in the UK, Europe and North America. It is designed to assess safety and tolerability, how the drug behaves in the body (pharmacokinetics), and its biological effects (pharmacodynamics).
In the UK trial sites will be at Sheffield Teaching Hospitals NHS Foundation Trust and University College London Hospitals.
Participants will receive either TRCN-1023 or placebo, with 24 weeks of follow-up. The trial also incorporates biomarker analysis and digital assessments of movement and speech, aimed at reducing patient burden.
The LAUNCH ALS study in China is expected to enrol around 25 participants with similar eligibility criteria.
It is being conducted in partnership with Tenacia Biopharmaceutical and led by Dr Yilong Wang at Beijing Tiantan Hospital, one of China's leading neurological centres.
Dr Wang said: "People with ALS urgently need innovative treatments beyond today's limited options. TRCN-1023's biological rationale, potency and durability make it an exciting candidate to bring into the clinic."
Rick Fagan, Director of Biopharm at UCL Business, said: "When Trace Neuroscience launched in 2024, they did so with a milestone Series A funding round of over $100m, indicating investors' excitement for UNC13A as a therapeutic target.
"We share that excitement and are proud to support Professor Fratta and the entire Trace Neuroscience team as this therapeutic now moves into clinical trials.
"That's what technology transfer is all about - getting world-leading research from the university out into the world where they have the potential for bringing positive impacts."
