Portait of Duchenne – repurposing existing drugs for DMD

Steve J. Winder, PhD

Professor of Molecular Cell Biology, Director of Postgraduate Teaching, Director of External Relations, Department of Biomedical Science, The University of Sheffield, United Kingdom

In this sixth interview of our series “Portrait of Duchenne,” La Force DMD talks with Steve Winder, Professor of Molecular Cell Biology, Director of Postgraduate Teaching, Director of External Relations, Department of Biomedical Science, The University of Sheffield, United Kingdom. He has been working on aspects of Duchenne muscular dystrophy (DMD) for more than 20 years. He has worked on this project for the last 3 or 4 years.


Why repurpose existing drugs for DMD?

Developing a brand-new drug takes an enormous amount of time, money and effort. Delays and barriers mean that the translation of a promising molecule into an approved drug often takes more than 14 years. It is crucial to advance strategies to reduce this time frame, decrease costs and improve success rates. Drug repurposing or re-positioning is one such strategy. This is what Steve Winder and his team of researchers are exploring; in this case, cancer drugs that affect muscle and which may be useful in the treatment of DMD.


In the video, Professor Steve Winder answers our questions about repurposing existing drugs for DMD.

  • Can you explain the process of drug repurposing?

Ok, so repurposing is taking a drug that’s already been approved for clinical use in one disease and working out whether it’s suitable and effective to use in another disease. A good example would be something like aspirin, which you take for headaches because it’s a painkiller, but these days a lot of people also take the aspirin to prevent heart attacks, because it thins the blood. So, the drug has a primary effect, but it also has what I would call a side effect. And sometimes these side effects can be really useful. So, this is what we are trying to do with a series of drugs that might be useful in treating Duchenne muscular dystrophy. So, in this case, it’s cancer drugs, but they have other effects in the muscle, which may be useful for the treatment of Duchenne muscular dystrophy.


  • What drugs are you repurposing in your current research?

So, these drugs that we’re working with are a group of anti-cancer drugs that are mostly used to treat chronic myeloid leukemia, which are genetically based leukemias that occur reasonably common. And, the advantage of these drugs is, because the disease, as its name says, is chronic myeloid leukemia, the disease is long-lasting, so the drugs are given for long periods of time, So, they’ve been designed to be well-tolerated, or the ones that are in clinical use are well-tolerated and can be given for, you know, 10s of, well, there are examples, certainly, of people being given these drugs for 10s of years. So, from that point of view, if you were going to treat a boy with DMD, it would probably be a life-long treatment, so they need to be well-tolerated, low side effects, and so on. So, these drugs would be particularly suited to that.


  • What effect could this approach have for DMD?

So, these drugs are inhibitors of signalling processes in the muscle that are altered when dystrophin is absent. The drug is not going to reverse the disease. If it were to work 100%, it would stop the disease from getting any worse. That’s the best it could do. But if you started treatment early, then obviously, you would preserve most of the muscles for the boys. And they act on inhibiting signalling pathways that are turned on aberrantly in the muscular dystrophy process. So it’s targeting things directly in the muscle that are altered as a consequence of the loss of dystrophin in the muscle tissue.


  • How long before this type of treatment is available?

We need to satisfy ourselves in the preclinical stages. So this is working with animal models of the disease, such as the MDX mice that have a mutation in the dystrophin gene, the same as boys with Duchenne muscular dystrophy. But the drugs that we’re testing (must) work as we expect them to work and actually have some benefit in the mouse before we then have the confidence to actually go forward and use them in boys with Duchenne muscular dystrophy in a proper clinical trial.


  • How do you envision the future for people with DMD?

In the last five years, even in the last two years, there’s just been an explosion of new potential treatments for Duchenne: some of which people have been working on for a very long time and others which have really just almost come out of nowhere. So, I think, in terms of potential treatments for Duchenne, they, I think, are looking really, really, really positive. I mean, when I originally started work on this, the prospects for treatment seemed completely bleak and no hope 20 years ago, but now, there are all sorts of things, different approaches. I am confident, in the next few years, we’ll see real benefits to lots of boys with Duchenne.



Interesting links

About The University of Sheffield

About drug repurposing for DMD


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We thank Action Duchenne, who received us with open arms to conduct a series of interviews.

More information about the next event: conference 2017




Portait of Duchenne – Edasalonexent: The potential to modify DMD

Joanne M. Donovan, MD, PhD

Chief Medical Officer at Catabasis Pharmaceuticals, Cambridge, Massachusetts, USA

In this fifth interview of our series “Portrait of Duchenne,” La Force DMD talks with Joanne Donovan, Chief Medical Officer at Catabasis Pharmaceuticals. She has been working on a treatment for DMD called edasalonexent (formerly known as CAT-1004). She earned her MD at Harvard Medical School.


Understanding how edasalonexent works

Edasalonexent (CAT-1004) is an investigational oral drug that targets NF-ĸappa B (NF-ĸB). What is NF-κB, and how does its inhibition benefit patients with Duchenne muscular dystrophy (DMD)? NF-kB is a protein complex that controls the transcription of DNA. In people with DMD, the absence of dystrophin, combined with mechanical stress in muscle, leads to an activation of NF-ĸB. When activated, NF-ĸB transcribes proteins that drive muscle damage and prevent muscle regeneration. Ultimately, the mission of edasalonexent is to prevent NF-kB from being activated. Inhibiting NF-kB can potentially protect muscles and have an important disease-modifying effect in DMD. This treatment works in patients with any mutation for DMD.


Updated information about clinical trials

Parts A and B of the MoveDMD trial with edasalonexent (CAT-1004) in DMD are complete. Part A reported that edasalonexent was well-tolerated with no significant safety issues. Catabasis has reported that, in Part B, with 12 weeks of edasalonexent treatment, numerical improvements were observed in well-established and pre-specified functional assessments. These statistical improvements in the functional assessments demonstrated reductions in the rate of functional decline in both placebo-controlled and crossover analyses. The crossover analysis compared changes during an off-treatment period to edasalonexent treatment for boys who were also in Phase 1 of the trial. The primary endpoint in the 12-week Phase 2, which was an exploratory MRI biomarker endpoint, was not met. Edasalonexent was well-tolerated with no safety signals observed. Edasalonexent is currently in the open-label extension of the MoveDMD trial with results expected in Q3 2017. Catabasis anticipates announcing plans for a Phase 3 trial in the second half of 2017.



This video was recorded in November 2016, Dr. Joanne Donovan answers our questions about edasalonexent (CAT-1004)


What is edasalonexent (CAT-1004)?

Yes, so we have been working on edasalonexent, which is an NF-kB inhibitor. And the reason that we are targeting NF-kB for Duchenne muscular dystrophy is that that protein is central to the progression of the disease. In infants, NF-kB is active in the muscle, so we know it happens very early before there is progression, and while every boy lacks dystrophin in all of their muscles, we know that the muscles that are subjected to more mechanical stress have faster disease progression. So, we also know that NF-kB is activated by mechanical stress in muscles. So, if we can protect, if we can inhibit NF-kB, we can potentially protect the muscles and have a very important disease-modifying effect.


How do we take it?

It is an oral medicine, and the boys take it as small gel capsules. And even the boys who are aged 4 to 7 in the study have been able to take the capsules.


About clinical trials

This is an initial phase 2 study, and it’s to understand whether the drug affects muscles. And it’s a small study: it’s 31 boys, and we have done this at five sites in the United States. What, with the results of that study, we are then looking to plan studies – a more significant phase 3 study, which is a global study, again in 4 to 7-year-old boys that are not yet on steroids, and we are also potentially looking to start a study next year in non-ambulatory patients that are no longer on steroids. We know that there are a significant number of young men who are no longer on steroids after they become non-ambulatory. So, we’re looking at those two patient groups, and we anticipate that we will start those studies next year in 2018.


About the connection with the DMD community

I have now met many boys, many many parents, and it makes an enormous difference. At Catabasis, we have been fortunate to have several parents come in – we’re a small company – and go in and talk to the whole company. And it’s incredibly meaningful for the company. It gives us very much an understanding of the urgency of why we need to move things forward as fast as we can. So, we appreciate the opportunity always to talk to you as parents and to meet patients, because it does drive us, which is essential.


Interesting links

About Catabasis Pharmaceuticals

Up-to-date information about clinical trials

About NF-kb


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We thank Action Duchenne, who received us with open arms to conduct a series of interviews.

Special Thanks to Daniel K Cooper and Allain Lagadic