NeuroVoices: Emma Ciafaloni, MD, on Mounting Progress in the Neuromuscular Field, Duchenne Muscular Dystrophy

Emma Ciafaloni, MD

The 2023 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference, held March 19-22, in Dallas, Texas, features a range of preclinical, translational, and clinical research across neuromuscular disorders in the hopes of finding better care and treatments for the community. Among the conditions covered is Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness due to the alterations of a protein called dystrophin. Currently, all of the therapeutic strategies to restore dystrophin in patients with DMD involve semifunctional, biochemically abnormal types of dystrophins and are not the full-length protein.

With the breakthrough of Novartis’ Zolgensma in 2019, the first gene therapy to treat spinal muscular atrophy, many in the field ponder whether gene therapies could have place elsewhere. Currently, the DMD community is awaiting the FDA’s decision on delandistrogene moxeparvovec (also known as SRP-9001), Sarepta Therapeutics’ investigational gene therapy. At the meeting, Emma Ciafaloni, MD, an expert in neuromuscular diseases, gave a talk on the current and emerging gene therapies in DMD, and whether clinicians can expert more in the coming future. As part of a new iteration of NeuroVoices, Ciafaloni provided perspective on the progress made in the field, the conversations surrounding gene therapies, and the ongoing challenges that still need to be addressed.

NeurologyLive®: What stands out about MDA 2023?

Emma Ciafaloni, MD: This is one of the most focused and exciting conferences. MDA has been around for such a long time, supporting research in very rare neuromuscular diseases for many years. At this particular conference, when there are so many new treatments finally coming to patients and their families, it is very exciting. Part of the big discussions, at least in the field of Duchenne muscular dystrophy, at this conference, have been about gene therapies potentially coming into a commercial phase. But of course, there have been many other treatments that are in different phases of development. The whole field in general is at an exciting time.

What are some of the main takeaways from your presentation?

The integrated session focused on gene therapy across a variety of neuromuscular diseases. We're learning very rapidly in the field, and one of the focus is to have shared learning across diseases. We have the very successful story of gene therapy in SMA, so there has been quite a bit of learning from that first in vivo gene therapy for that disease. Now, Duchenne or limb girdle muscular dystrophy may perhaps be next to see these therapies in the near future.

Above all, we want to learn across diseases. In that session, I summarized where we stand in terms of gene therapies or gene-based therapies for Duchenne muscular dystrophy. It will be a review of the different program and different phases of development. There are at least 3 companies, probably more in the near future, that are going into human clinical trials for gene therapy. The closest one, or furthest in development, is Sarepta. There has been a lot of talk at this conference about the PDUFA for delandistrogene moxeparvovec (Sarepta) at the end of May, but there are other trials as well that are already in phase 3 and advancing.

Over these next 3 days, the longitudinal session also talks about how to translate gene therapy from clinical trials into real life and in the clinics. There has been a lot of brainstorming about that, which is so important to be successful in terms of access, and safety and efficacy. Once you translate into the real life, there is a whole different set of priorities.

Are there any major challenges that need more attention in the neuromuscular space?

There is still plenty of good work to be done. There are a lot of questions biologically that we are acquiring a lot of data for, but those will take time, like durability and redosing and so forth. The other important question is how to translate findings effectively and safely from clinical trials to real life clinical practice. These are rare diseases, and disease modifying treatments are so new in the field. How do we roll them out in an equitable and just way for all patients who are a candidate for this treatment. There has been quite a bit of talking about that, access to treatment. Just because a treatment is FDA approved, doesn't mean that access is going to be immediate and universally easy for all patients. That obviously opens up some ethical issues that are also on the table for clinicians to approach. How we're going to deliver this treatment to as many patients as possible in a in a just way?

Is there anything else you’d like to note?

After 50 years of amazing lab based research for gene therapy, it’s so exciting to be able to witness and read about it. I feel extremely fortunate. I know my colleagues in the field feel so privileged that we're now putting these treatments into babies, children, and seeing the reward, the results, the efficacy, and the transformative effect of this treatment in our patients. Also, the joy that these therapies bring to the patients, the family, and to us. If you had told me when I went to medical school that we will have a treatment that will make such a transformative impact, it would have been hard to believe 20, 30 years ago. Now we're really seeing extraordinary results. It's a very exciting time for the older neuromuscular experts just to be able to witness it. And for the younger experts, it probably feels very inspiring because their futures will only continue these series of successes.

Transcript edited for clarity.