In the UK, about 100 boys are born each year with Duchenne muscular dystrophy (DMD), a serious condition that causes progressive muscle weakness.[1] Unfortunately, there is no cure – and while life expectancy is increasing, most people with DMD only live into their 20s or 30s. Professor Francesco Muntoni of UCL Great Ormond Street Institute of Child Health is investigating whether combining gene-based therapies with existing medications could improve their effectiveness at targeting the root cause of the disease. His laboratory work could help unleash the full potential of these cutting-edge treatments, transforming the lives of many children and their families affected by this devastating condition.
This project is jointly funded by Action Medical Research and LifeArc.
How are children’s lives affected now?
Children with DMD have a faulty gene which means they don’t make enough – or any – of a protein called dystrophin, which is important for keeping muscles healthy. As a result, they will experience a range of debilitating symptoms that usually start in early childhood and gradually worsen over time.
“During the early stages, some boys with DMD are already late in acquiring basic movements like walking, as well as learning to talk,” says Professor Muntoni. “By their early teens, most will need to use a wheelchair – and sadly, many don’t live past their thirties.”
A cutting-edge treatment approach, called antisense oligonucleotides (AONs), involves delivering tiny pieces of genetic material into muscle cells. These molecules are precisely designed to bypass the effects of certain faults in the dystrophin gene, allowing the production of a functional version of the dystrophin protein.
“These advanced gene-based therapies aim to restore sufficient levels of the protein in muscle cells, alleviating symptoms and slowing disease progression – dramatically improving the lives of children born with DMD,” says Professor Muntoni.
How could this research help?
“We’re aiming to develop a new treatment strategy for boys with DMD – by combining AONs with other drugs to improve their effectiveness at boosting dystrophin levels,” says Professor Muntoni.
Although AONs show great potential, their effectiveness has been limited so far by the low levels of the protein produced in the muscle cells of DMD patients. Early laboratory experiments suggest that combining these therapies with other drugs called histone deacetylase inhibitors (HDACi) might help address this challenge.
“Our next step is to test various combinations of AONs and HDACis on patient cells to determine which is most effective at increasing dystrophin protein production,” says Professor Muntoni.
By focusing on therapies that are already in use or have undergone extensive clinical trials, the team hopes to accelerate the process of bringing the most promising treatment strategies to children with DMD.
Currently, at least one in three boys with DMD could potentially benefit from this treatment approach, but as new AONs are developed, that number is likely to increase.
Research table
Project details
| Project Leader | Professor Francesco Muntoni, FRCPCH FMedSci |
| Location | Dubowitz Neuromuscular Centre, UCL Great Ormond Street Institute of Child Health |
| Project Team | Dr Rachele Rossi, PhD |
| Other Locations | Dubowitz Neuromuscular Centre, Developmental Neuroscience Department, UCL Great Ormond Street Institute of Child Health |
| Grant Amount | £175,252 |
| Duration | 24 months |
| Grant Code (GN number) | GN3042 |
References
- NHS website, Muscular Dystrophy: https://www.nhs.uk/conditions/muscular-dystrophy/ [website accessed 24 September 2024]
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