This study will look at the effect of combining three drugs for the treatment of DMD. It will determine whether there is an advantage to combine these compounds and at what dose.
The drugs are tamoxifen, L -citrulline and metformin.
Tamoxifen is a licenced breast cancer treatment, has been shown to be an effective treatment in initial studies. It has been shown to slow down the damage to the heart, muscles and diaphragm as well as improve motor functions. Repurposing medicines that are already approved for use and have been tested on humans is hugely advantageous as information on their use and effect on humans 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.
A recent pilot study showed DMD patients respond well to a combination of metformin, a drug well known to treat type 2 diabetes, along with L-arginine. The combination was shown to improve blood flow to muscles during exercise. L-citrulline, a food supplement, is the pre- cursor to L-arginine.
The study will also look at whether there is an advantage to combine these compounds with Prednisolone, which is 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.
It is great for Alex’s Wish to be able to work with Dr Dorchies and Duchenne UK to ensure that money invested goes into projects that have a real impact. This project is particularly exciting as it is looking at combining treatments potentially resulting in improved benefits for those with DMD.
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.”
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.
Alongside Duchenne UK, as well as Alex’s Wish, Joining Jack and family funds Chasing Connor’s Cure, Help Harry, Jack’s Mission and Team Felix have all supported this project. Together we are stronger.