Researchers from the University of Sheffield collaborated with the Cell and Gene Therapy Catapult to introduce a novel gene therapy program that could set the stage for new treatments for neurodegenerative diseases.
Image Credit: University of Sheffield.
The groundbreaking research has been awarded £513,141 from LifeArc and the Motor Neurone Disease Association to investigate the viability and efficiency of an ambitious gene therapy program for the treatment of motor neurone disease (MND) and frontotemporal dementia (FTD) patients with underlying mutations in a causative gene called C9orf72.
In case the program turns successful, it could pave the way for pioneering research into future clinical trials for one of the most common forms of incurable neurodegenerative diseases in the next few years.
The study led by the University of Sheffield’s Institute for Translational Neuroscience (SITraN) is headed by Dr. Guillaume Hautbergue, Head of the RNA Biology Laboratory, in collaboration with Professor Mimoun Azzouz and Professor Dame Pamela Shaw.
No one has yet attempted to prevent these repeated sequences of RNA from leaving the cell’s nucleus and it opens up new areas of investigation for gene therapy. It is an exciting time for biomedical research and the development of novel treatments for incurable diseases such as MND.”
Dr Guillaume Hautbergue, Head of RNA Biology Laboratory, Institute for Translational Neuroscience, University of Sheffield
Published in Nature Communications, the early-stage study enabled Dr. Hautbergue and his group to identify why the repeated RNA sequences could leave the cell’s nucleus to cause cell death.
The researchers found a specific protein known as SRSF1 that attaches to the pathological repeated RNA molecules and carries them out of the cell center, thus effectively overriding the gatekeeping machinery inside the nucleus by opening a back door.
Furthermore, the team has demonstrated that the number of rogue RNA molecules escaping into the cell’s cytoplasm can be reduced by decreasing the SRSF1 protein or modifying its composition, which makes it unable to interact with the cell’s export machinery.
“This is a completely new approach to tackling the most common type of motor neurone disease,” added Dr. Guillaume Hautbergue.
Financially supported by LifeArc and the MND Association, the new study will be performed in collaboration with the Cell and Gene Therapy Catapult, an independent center of excellence to promote the growth of the UK cell and gene therapy industry.
The Cell and Gene Therapy Catapult will offer an in-depth non-clinical safety strategy and regulatory advice to lead the team at the University of Sheffield through interactions with the Medicines and Health Regulatory Agency for the prospective commercialization of an advanced therapy medicinal product.
The progress of this scientific breakthrough from the University of Sheffield and the support for this programme by leading investors and charities such as LifeArc and the MND Association, is testament to the UK research excellence and favourable ecosystem for cell and gene therapies.”
Matthew Durdy, Chief Executive Officer, Cell and Gene Therapy Catapult
“We welcome the opportunity to be part of this program and look forward to working with the University of Sheffield to help advance their innovative gene therapy technology into the clinics,” added Durdy.
We are delighted to be joining with LifeArc in supporting this innovative research programme at one of the world’s leading centres for MND research. Gene therapy for neurodegenerative diseases, such as MND, has had its ups and downs over the past two decades, but the field is now enjoying a renaissance. There is a clear route to clinical trials if the outcomes of this new study are positive.”
Dr Brian Dickie, Director of Research Development, MND Association
According to Dr. Melanie Lee CBE, Chief Executive Officer of LifeArc, a self-funded medical research charity, “Funding this innovative and promising research reflects LifeArc’s focus on working with partners to advance pioneering medical research into life-changing treatments and diagnostics for patients.”
“This gene therapy approach, focused on preventing motor neurone toxicity, is the latest in a series of initiatives we are proud to be part of to drive research into practical treatments for this fatal and brutal condition,” concluded Dr. Lee.
Hautbergue, G. M., et al. (2021) SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits. Nature Communications. doi.org/10.1038/ncomms16063.