Developing an animal model to test therapies for certain types of muscular dystrophy
Dr Susan Brown, Royal Veterinary College will supervise a student to study two conditions caused by changes in a gene called FKRP. It is not well understood why a change to one part of the FKRP gene can cause a very severe form of congenital muscular dystrophy while a mutation in a different place can cause a much milder form of limb girdle muscular dystrophy (type 2I). They will use an animal model to try to better understand these conditions but also to test possible therapeutic approaches.
Contents:
- What are the researchers aiming to do?
- How will the outcomes of the research benefit patients?
- Grant information
- Further information and links
What are the researchers aiming to do?
Dystroglycan is a protein that forms an important link between muscle cells and their surroundings - this gives the muscles strength. Dystroglycan is also important for brain development and function. In order for dystroglycan to function correctly, sugar molecules need to be added. Defects in at least six different sugar-adding enzymes have been shown to cause several types of muscular dystrophy which have been collectively termed the 'dystroglycanopathies'.
Two of the dystroglycanopathies - limb girdle muscular dystrophy type 2I (LGMD2I) and congenital muscular dystrophy type 1C (MDC1C) - are caused by mutations in the gene that carries the instructions for 'Fukutin Related Protein' (FKRP). Although both conditions are caused by mutations in the same gene, the conditions themselves are quite different. Congenital muscular dystrophy type 1C is a severe muscle disease with the symptoms evident from birth. Congenital muscular dystrophy caused by a mutation in the FKRP gene can sometimes also affect the brain. LGMD2I tends to be quite variable in severity and the age of onset is generally between ten and twenty years of age.
Dr Brown has developed a mouse model for LGMD2I and, with the help of her PhD student, aims to determine why one mutation in FKRP might cause a relatively mild condition while a different mutation can cause a severe condition that affects not only the muscle but also the brain. They will examine how the disease progresses and the changes that take place in the muscles.
Using the mouse model, the researchers will also test potential therapies for these conditions. For example, they plan to investigate whether increasing levels of one of the other sugar-adding enzymes might be able to compensate for FRKP and restore some of the function of dystroglycan.
How will the outcomes of the research benefit patients?
This work will help to increase understanding of the effect of mutations in the FKRP gene. Having an animal model to study will allow Dr Brown to chart the progress of the condition and how it affects the muscle cells themselves. This can be difficult to achieve using human muscle biopsies as they give you information on only one point in the progression of the disease. Since it is an invasive procedure, it is not possible to take multiple samples throughout the person's lifetime. This work may also lead to a therapy in the future as the team plans to use the animal model to test a potential therapy for LGMD2I and congenital muscular dystrophy type 1C.
Grant information
Project leader: Dr Susan Brown
Location: Royal Veterinary College, London
Conditions: Limb girdle muscular dystrophy, congenital muscular dystrophy
Duration: 4 years
Total project cost: £113,810
Official title: Validation of an animal model for therapeutic testing in LGMD2I
Further information and links
Download our factsheet on limb girdle muscular dystrophy 2I
Read more about congenital muscular dystrophies
Read the latest research news for congenital muscular dystrophy and limb girdle muscular dystrophy
Find out more about the other research we fund
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