DMD research

Duchenne UK funds further research to understand the benefits of repurposed drugs in combination as a treatment for DMD

Duchenne UK is pleased to announce funding of £200,000 for Dr Olivier Dorchies at the University of Geneva, towards a 2-year pre-clinical study into a combination therapy for Duchenne Muscular Dystrophy.

The study will investigate the effect of combining tamoxifen, L-citrulline and metformin for the treatment of DMD. Specifically, it will determine the optimum doses of L-citrulline and metformin, to combine with tamoxifen, for maximum efficacy and safety. The study will also determine whether there is an advantage to combining these compounds, at those doses, with prednisolone, the most commonly prescribed steroid for the treatment of DMD.

The study is important because it has the potential to provide us with the essential pre- clinical data to determine effective dosing in patients at a later stage. Currently we do not know the appropriate and relative doses that may prove effective.

Tamoxifen, a licenced breast cancer treatment, has been shown to be an effective treatment in dystrophic mice (1). It has been shown to slow down the damage to the heart, muscles and diaphragm as well as improve motor functions. Duchenne UK is already funding and supporting a large stage 3 clinical trial for the use of tamoxifen in DMD, which will start this year.

Repurposing medicines that are already approved for use and have been tested on humans is hugely advantageous as information on their pharmacology, formulation and potential toxicity already exists. This may dramatically reduce the time it can take to get medicines into the clinic to be tested for new indications on patients.

Commenting on the grant award, Dr Dorchies said: “In the recent years, there have been a significant interest in repurposing well-established human medicines for DMD. We showed that tamoxifen, one of these “old drugs”, is very potent in dystrophic mice and clinical trials are about to start in DMD boys. With the support of Duchenne UK, we are now entering a new era of pharmacological therapy for DMD: evaluating combination of tamoxifen with other carefully selected drugs that have complementary modes of action should help fighting the symptoms of DMD from different angles at the same time, potentially resulting in much improved benefits for the patients than any drug used alone.”

Alex Johnson and Emily Crossley, Co-founders, CEO of Duchenne UK said: “Duchenne UK is committed to developing repurposed medicines as potential treatments for DMD, and this project follows on from previous work on combination therapies. We are delighted to be working with Dr Dorchies and his team.”

A recent pilot study showed DMD patients respond well to a combination of metformin, a drug well known to treat type 2 diabetes, and L-arginine (2). The combination was shown to improve blood flow to muscles during exercise. L-citrulline, a food supplement, is the pre- cursor to L-arginine. Tamoxifen and metformin/L-citrulline work through entirely different biological mechanisms, which raises the possibility that combining them may prove additive in terms of effect.

The work for this study will be performed at the Pharmaceutical Biochemistry group, headed by Prof. Leonardo Scapozza at School of Pharmaceutical Sciences at the University of Geneva, Switzerland. The work has the potential to become an alternative or additional treatment to steroids. Tamoxifen and metformin are already licenced drugs and L-citrulline is an established food supplement.

We would like to thank our partner charities Alex’s Wish and Joining Jack and family funds Chasing Connor’s Cure, Help Harry, Jack’s Mission and Team Felix for supporting this project.

1. Dorchies, Olivier M. et al. (2013) The Anticancer Drug Tamoxifen Counteracts the
Pathology in a Mouse Model of Duchenne Muscular Dystrophy, The American Journal of Pathology, Vol 128
2. Hafner P, Bonati U, Erne B, Schmid M, Rubino D, Pohlman U, et al. (2016) Improved
Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept- Study, PLoS ONE 11 (1).

Other reading:

Hesham M. Ismail, Olivier M. Dorchies and Leonardo Scapozza. (2018) The potential and benefits of repurposing existing drugs to treat rare muscular dystrophies, Exp. Opin. Orphan Drugs (in Press): https://doi.org/10.1080/21678707.2018.1452733.

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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 treatment or 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 Manger, Duchenne UK E: [email protected]

Published on 26 March 2018

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