Facioscapulohumeral muscular dystrophy (FSHD) is the third most common inherited muscular dystrophy. Whilst it does not shorten lives, it drastically impacts the quality and to date there is no cure or targeted treatment.
FSHD commonly causes muscle wastage in the face (facio), shoulders (scapula) and arms (humeral). However, some people living with FSHD can end up requiring a wheelchair or leg braces (30% and 10% respectively) if the muscle weakness spreads to their legs. Some people living with FSHD can also experience loss of hearing and vision. FSHD symptoms can vary substantially from one person to the next, making management and understanding of the condition challenging.
What was the aim of the study?
This research, funded by MDUK, was carried out by Professor Peter Zammit and his team at King’s College London. They investigated how the known genetic causes of FSHD translate into its symptoms, focusing on metabolism and mitochondria. Metabolism is broadly how your body uses the energy from your food, and mitochondria are microscopic structures within cells that convert that energy into a form you can use. The study aimed to identify new targets for treatments for the future.
What are the results?
They found that the key components of mitochondria that control metabolism are different between people with FSHD and those without it. For example, people with FSHD were found to have more of a structure called complex I. They also observed a build-up of harmful chemicals from the dysfunctional mitochondria, which was associated with poor muscle growth in FSHD patients. Laboratory FSHD models subsequently showed these harmful chemicals could overwhelm the sensitive biological processes in the muscle, causing it to waste.
Additionally, they demonstrated that the muscles from people with FSHD have an impaired response to low oxygen because of increases in expression of the DUX4 gene, which is the gene that is altered in people with FSHD. This is crucial because oxygen levels in muscles can be naturally low during day-to-day activity. The genetic changes also negatively affect the development and structure of muscle, especially when it is exposed to low oxygen. Furthermore, muscle samples from people with FSHD were shown to have a more disrupted structure and greater build-up of damaging chemicals compared to those without the disorder when exposed to low oxygen. Therefore, the muscles of FSHD patients are less able to cope with low oxygen, causing muscle damage and wastage.
Finally, three compounds called antioxidants, including vitamin C, Coenzyme Q10 and mitoTEMPO, which can reduce the accumulation of the harmful chemicals upon damage to mitochondria, were tested for their potential in FSHD treatment. They all benefited muscle structure and development.
What are the future benefits of this research?
This research has identified potentially novel therapies for treating FSHD, which could alleviate symptoms and be combined with other effective treatment options. Additionally, the biological causes for FSHD have been thoroughly investigated, providing a plethora of new data from which exciting, cutting-edge research can be conducted to improve the lives of those living with the condition.
If you are interested to know more about this research, the research article is accessible from this link.
‘What’s new in research’ is our new monthly blog series that will feature recent advancements in research into muscle-wasting conditions. Each month, a research article will be summarised for you by our research communications volunteers, all of whom have backgrounds in various fields of research.
This piece is written by Ben Futcher. Ben is studying for a doctorate (DPhil) in oncology at the University of Oxford, researching cell pathways involved in cancer. He got involved in writing for MDUK because he saw the effects of muscular dystrophy condition on classmates through primary school and wanted to use his understanding of science to help better communicate the exciting research being done to understand and treat these complex conditions.