In 2015, Drs Stan Froehner and Nick Whitehead at the University of Washington, published a paper on the potential benefits of statins in DMD. They tested a commonly used statin called Simvastatin. In early pre-clinical models of DMD, short term dosing showed reduced skeletal muscle damage and enhanced muscle function.  Long-term dosing in the same models showed an overall improvement in muscle health. 

Duchenne UK has been supporting the development of Simvastatin for a treatment for DMD. In 2016 we supported an application to the TREAT-NMD Advisory Committee for Therapeutics (TACT) to review a potential clinical trial for Simvastatin.

The Summary can be viewed here.

One of the recommendations made by TACT was for Simvastatin to be tested in an independent lab. This is common in drug development because it’s important that promising discoveries are re-tested in other laboratories to make sure the findings are robust enough to be replicated.

So, we are now investing €35,745 to validate Dr Froehner’s work in a different lab. Dr Annemieke Aartsma-Rus at Leiden University Medical Centre will perform this replication study.  Dr Aartsma-Rus and her colleagues have liaised closely with Dr Froehner to ensure the same conditions are used. Solid Biosciences will perform analysis of plasma simvastatin levels.  

This is an important study and we hope Dr Aartsma-Rus can replicate the results found by Dr Froehner so we can then discuss with him the next stage of the research.

Duchenne UK has also funded a further study to test Simvastatin against other commonly used statins to test if Simvastatin is the best product to take forward for more testing.

In 2016 Duchenne UK funded a repurposing project with Professor Dominic Wells at the Royal Veterinary College to investigate a number of compounds, including Simvastatin.

The results from this project were disappointing as they did not match the findings of Drs Stan Froehner and Nick Whitehead’s work. However further analysis revealed that Simvastatin was barely detectable in the plasma of the mice (only 0.025% of the expected level). This is significantly below what is considered a therapeutic dose. We do not know why this was the case, but it may relate to poor uptake of the drug which was given in the food provided for the mice. This has made it all the more important for the work with Dr Aartsma-Rus to continue. 

Q&A:

What is Simvastatin:

Simvastatin, along with other statins, may provide skeletal and cardiac muscle function benefits in DMD patients.  Preclinical studies are underway to help characterise better the risks and benefits of statins in DMD and inform the optimal molecule to move into clinical studies. Mechanism: DMD is characterised by chronic inflammation, oxidative stress and fibrosis. Statins, which are already approved for cardiac indications, have been shown to inhibit these harmful processes.  In early preclinical models of DMD, Simvastatin reduced muscle damage and enhanced muscle function. 

Why is repurposing an important approach?

Testing existing medicines to see if they could be effective in treating diseases such as Duchenne Muscular Dystrophy is an exciting approach known as repurposing, and it’s something we are actively pursuing. The advantage of this approach, compared to the development of an entirely novel compound, is that the development time has the potential to be cut dramatically, because these medicines are already approved as safe for use in humans.

 

 

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NOTES FOR EDITORS

 

What is Duchenne Muscular Dystrophy?

Duchenne Muscular Dystrophy is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease.

Who are Duchenne UK? 

Duchenne UK is a lean, ambitious and highly focused charity with a clear vision: to fund and accelerate treatments and a cure for Duchenne muscular dystrophy. The charity has been formed by the coming together of Joining Jack and Duchenne Children's Trust, the two biggest funders of research in the UK in the last three years. Its president is HRH The Duchess of Cornwall. Its patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell. 

How to donate?

Duchenne UK is entirely reliant on donations to fund research for treatments and a cure to DMD. This can be done via:

  • Direct Debit – Duchenne Direct
  • Individual Donation – Donate
  • If you are a family or friend affected by DMD you can set up your own fund with Duchenne UK – Family and Friend Funds
  • Take part in one of our fundraising events – Events
  • Text DUCH10 £10 to 70070

For more information and interview requests:

Visit www.duchenneuk.org 

Molly Hunt – Communications Manager, Duchenne UK 

E: [email protected]