Understanding the variable clinical severity of LMNA-CMD

Dr Gisèle Bonne and her team at the Myology Institute in Paris aim to understand what leads to the wide range of clinical severity in people with LMNA-Congenital muscular dystrophy (LMNA-CMD). This research could help to inform clinical care and identify new therapeutic targets.
Dr Gisèle Bonne and her team at the Myology Institute in Paris aim to understand what leads to the wide range of clinical severity in people with LMNA-Congenital muscular dystrophy (LMNA-CMD). This research could help to inform clinical care and identify new therapeutic targets.

 

This project is co-funded by Muscular Dystrophy UK and Cure CMD – a collaborative partnership established to support world-class research in the search for treatments and eventually cures for LMNA-CMD.

 

 

 

 

What are the aims of the project?

Changes (mutations) in the LMNA gene cause a group of muscle-wasting conditions called laminopathies. People with laminopathies can be affected very differently – even if they have exactly the same LMNA mutation. In this research project Dr Bonne and her team will investigate why this is the case.

 

 

What will the researchers do?

The researchers will use next generation sequencing to search for changes within the DNA of people with laminopathies that may worsen (or lessen) the effect of the LMNA mutation, leading to more (or less) severe symptoms. These genetic changes are known as modifiers. The team will also investigate how these modifiers affect the function of muscle cells with LMNA mutations.

 

 

This research project will use valuable tools, such as the Congenital Muscle Disease International Registry (CMDIR), to learn about different mutations that cause LMNA-CMD and access samples that have been donated by people with the condition.

 

 

Why is this research important?

Information about modifiers will improve our understanding of what causes the symptoms of LMNA-CMD. Importantly, this will help clinicians and families to have a better idea of the clinical course (prognosis) of an individual’s CMD, and so more tailored care and management can be put in place. In the future, the information from this project may also help in the design of clinical trials and potential therapies. For example, if the researchers identify a ‘protective’ genetic modifier, they may be able to design a therapy that targets this.

 

 

How might this research impact on other neuromuscular conditions?

The laminopathies are a spectrum of muscular dystrophies that vary in severity and age of onset:

 

  • LMNA-CMD (severe congenital-onset)
  • Emery-Dreifuss muscular dystrophy (childhood-onset)
  • Limb girdle muscular dystrophy type 1B (milder, adult onset)

 

 

This project may identify modifiers that play a role in these conditions, helping us to better understand their symptoms.

 

 

Grant information

Project leader: Dr Gisèle Bonne

Institute: INSERM, Paris

Condition: LMNA congenital muscular dystrophy

Duration: Two years

Total cost (£): 150,000

Official title: Identification of genetic modifiers modulating the diseases severity of LMNA-CMD

 

 

For further information

Read more about Dr Bonne and some of the families supporting this project in our feature article

 

If you would like further details about this research project, please contact the MDUK Research Line on 02078034813 or email research@musculardystrophyuk.org

 

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