British gene therapy company Crucible Therapeutics, a spinout from the University of Sheffield, has emerged with £5 million ($6.1 million) in funding from Northern Gritstone and Argobio Studio. The company is developing gene therapies for neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), specifically targeting cases with the C9orf72 gene mutation.
Crucible emerged from the collaborative efforts of a team of experts from the University of Sheffield’s Neuroscience Institute, comprising Professor Guillaume Hautbergue, an expert in translational RNA biology; Professor Mimoun Azzouz, a specialist in translational neuroscience; and Professor Dame Pamela Shaw, Director of the Sheffield Institute for Translational Neuroscience (SITraN).
The company’s approach is based on the researchers’ work on a protein called SRSF1, which binds to pathological repeated RNA molecules and transports them out of the cell nucleus, effectively circumventing the nucleus’s gatekeeping machinery. The researchers also demonstrated that by reducing the SRSF1 protein or altering its structure to prevent interaction with the cell’s export machinery, it is possible to reduce the escape of rogue RNA molecules into the cell’s cytoplasm.
“I worked on the therapeutic target for more than 15 years, initially to study its roles from a discovery perspective, prior to realising its promising potential for the development of a novel gene therapeutics in close collaboration with the other founders,” said Hautbergue.
Building upon this research, Crucible has developed a gene therapy technology designed to target the SRSF1 pathway and yield therapeutic effects in patients with MND and FTD.
“Our novel therapeutic approach has made significant strides in our pursuit of transforming how these devastating diseases are treated and potentially achieving meaningful therapeutic impact,” said Dame Pamela. “Today marks an important milestone, which brings us closer to supplying transformative treatments to people with neurological diseases like MND and FTD.”
Crucible says that the new investment supports “essential development and manufacturing work” and will fund the company up to its first clinical trial.