Trace Neuroscience: a ray of hope in motor neurone disease

UNC13A may not be a household name, but the decline in people’s ability to produce this vital protein characterises almost all cases of motor neuron disease. This rapidly progressive neurodegenerative disorder which affects around 5,000 people each year in the UK leads to wasting, paralysis, and eventual death from respiratory failure within 3-5 years. With few treatment options, the search for an effective treatment couldn’t be more important.    

In order to prevent the loss of UNC13A, co-founders including Pietro Fratta, MD, PhD, Professor of Cellular and Molecular Neuroscience at University College London (UCL) and Aaron Gitler, PhD, Professor of Genetics at Stanford University, set about developing antisense oligonucleotides – nucleic acids that can act at the genomic level to target the mechanism by which UNC13 is lost and prevent further loss of  the key protein. 

By protecting UNC13A, an essential component for neuronal communication in the brain and spinal cord, healthy communication between nerves and muscle cells impacted by neurodegenerative disease can be maintained, thereby slowing the progression of motor neurone disease. 

Trace Neuroscience was formed to commercialise the cutting-edge research at UCL and Stanford and to take on the challenge of bringing a treatment through clinical trials. UCLB licensed the intellectual property exclusively from UCL to Trace Neuroscience and the company made use of UCLB’s support as we worked with Professor Fratta from an early stage to understand the technology, and with patent agents to secure patent filings to protect the discovery.  

Once IP was secured, UCLB helped find a commercial partner to support further development and testing of a therapeutic. Dr Caitriona O’Rourke, Business Manager at UCL Business (UCLB), says the efforts proved fruitful:  

“Third Rock Ventures (TRV), Trace and the team had in-depth discussions about the target and antisense oligonucleotide (ASO) technology and it was agreed that TRV was a fitting partner to move this ASO technology forward. UCLB worked with Trace to negotiate the contracts required for the collaboration to move forward and will continue to support the academic team and Trace to move this technology to the clinic,” she adds. 

Antisense oligonucleotides (ASOs) are short, synthetic sequences of RNA or DNA that bind to messenger RNA (mRNA) and are designed to be specific to a target sequence. In the central nervous system, UNC13A is expressed in nerve tissue and plays an important role in maintaining healthy transmission of nerve impulses.  

The ASOs are still in the pre-clinical phases and are yet to be tested in patients, but UCLB looks forward to following Trace as it progresses the ASOs through pre-clinical phases and into clinical trials. 

Investors have clearly recognised the potential for ASOs to help the many thousands of patients around the world each year. The $101m financing, nearly unprecedented in the bio sector, was led by Third Rock Ventures and included participation from Atlas Venture, GV and RA Capital Management. 

Professor Fratta said: “This large funding round was pivotal for us to rapidly translate this science into a life-changing medicine and advance our lead programme towards the clinic. UNC13A is critical for neurons to communicate amongst each other and with muscles, and is lost in nearly all ALS cases. Being able to re-establish this is groundbreaking.” 

Could this mark a turning point for other neurodegenerative diseases? While the current focus is motor neuron disease, UNC13 also plays a role in frontotemporal dementia (FTD) and Alzheimer’s disease. “Restoring UNC13 could be a therapeutic option for these conditions but further research is needed to confirm this,” O’Rourke concludes.