Professor Francesco Muntoni and his team at University College London will develop molecular patches that could be a potential treatment for people with Ullrich congenital muscular dystrophy. This research will also help to further enhance molecular patch technology, which will be beneficial for the neuromuscular field in the long-term.
Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) are known as collagen VI-related myopathies, as they are caused by mutations in genes that produce collagen VI protein. This protein forms networks around our muscle cells and acts as a scaffold to hold and support them. In someone with UCMD or BM, collagen VI is faulty or absent, which means that their muscle cells are not supported properly and become damaged over time.
Most of our genes are inherited in pairs; one from our mother and one from our father. Everyone with BM and most people with UCMD have one healthy copy and one faulty copy of a particular collagen VI gene. This is known as ‘dominant’ inheritance, as the faulty copy overrides the healthy one and disrupts collagen VI production.
What are the aims of the project?
The primary aim of this project is to develop molecular patches that switch off or ‘silence’, or correct the faulty copy of the collagen VI gene. This aims to restore the production of collagen VI protein in people with UCMD or BM and stabilise or at least slow down the progression of the condition.
Some of the molecular patches will be linked to short protein fragments called peptides. These peptides help the molecular patches to get inside cells, thus improving their delivery into muscle and other tissues.
Professor Muntoni and his team will design molecular patches targeting four of the most common UCMD mutations. They will test them in cells originating from people with UCMD and evaluate their effect on collagen VI production.
The researchers will also test some of the molecular patches in a new mouse model of UCMD. This will be done in collaboration with Professor Bonnemann and his team at the NIH, USA (read more about Prof Bonnemann’s project).
Why is this research important?
Currently there is no effective treatment for UCMD or BM. This research could be an important step towards a treatment that addresses the genetic cause of these conditions.
Although molecular patches are now in clinical use for some muscle-wasting conditions, there are problems associated with their delivery to muscles and other target organs. This project will help to address this by linking the molecular patches to peptides and other novel advanced technology in this field. Enhancing the technology in this way could lead to better therapeutic outcomes.
How will the outcomes of this research benefit people with UCMD?
This project will test the effectiveness of molecular patches in cell and mouse models of UCMD. This pre-clinical research is essential for new drugs or treatments to be able to advance to human clinical trials.
How might this research impact on other neuromuscular conditions?
The knowledge gained from this project could help to enhance molecular patch technology generally. This could be beneficial for several muscle-wasting conditions for which molecular patches are being developed, including Duchenne muscular dystrophy, spinal muscular atrophy, facioscapulohumeral muscular dystrophy and myotonic dystrophy.
Project leader: Professor Francesco Muntoni
Institute: University College London
Condition: Ullrich congenital muscular dystrophy, Bethlem myopathy
Duration: Three years
Total cost (£): 224,040
Official title: Developing antisense oligonucleotide therapy for collagen VI-related congenital muscular dystrophy
This research would not have been possible without individual donations, family fundraising activities, trusts and corporate support for our Ullrich CMD Appeal.
Donate now and help us ensure that effective treatments and expert care are available to all those living with collagen VI-related conditions, including UCMD. Thank you.