Advances in Myositis and Lingering Unmet Needs Ahead of MDA 2023

Tahseen Mozaffar, MD

Angela Lek, PhD

The Muscular Dystrophy Association (MDA) is set to hold its 2023 Clinical & Scientific Conference on March 19-22, at the Hilton Anatole in Dallas, Texas, and virtually via live stream.

MDA plans to host sessions on the latest research advancements and clinical achievements, with a particular focus on emerging technologies in genetic medicine this year. Marks noted that he is hoping to address unique needs for the development and regulatory oversight of gene therapies and genetic medicines. Today, it announced that Peter Marks, MD, PhD, a hematologist and oncologist who serves as the director of the Center for Biologics Evaluation and Research (CBER) at the FDA, will be the keynote speaker.¹

Additionally, the meeting will include a session focused on myositis, a group of rare conditions that result in weakened and ailing muscles, including Suur Biliciler, MD; Teerin Liewluck, MD; Thomas Lloyd II, MD, PhD; and Eleni Tiniakou, MD, as its speakers. In recent years, while gene and cell therapy has seen a boom in research and clinical trials, myositis has similarly seen a rapid track of advances, with an improved understanding of disease classification at the forefront.

Angela Lek, PhD, vice president for research at MDA, and the session’s chair Tahseen Mozaffar, MD, director of the Division of Neuromuscular Diseases at UC Irvine, sat down with NeurologyLive® to offer some insight into the plans for this session, and the latest in myositis management and care.

NeurologyLive^®: Why did MDA choose to focus on myositis specifically at this year’s meeting?

Angela Lek, PhD: This year, we want to shine a spotlight on myositis because in previous years, it hasn't received so much attention. We want to give it some traction, and so with that, I invited Dr. Tahseen Mozaffar, from UC Irvine, to chair a session specifically on myositis and he has hand-selected experts from the field to give talks on various aspects of myositis.

Tahseen Mozaffar, MD: Myositis has always been under the muscular dystrophy umbrella, but I think there have been a lot of new developments in myositis. They are improvements in subclassification of myositis. They are new entities that have come under the umbrella, especially immune mediated necrotizing myopathy—which is becoming quite common, at least from a muscle pathology point of view, but even on the clinical side. This new entity of immune mediated necrotizing myopathy is related to some of the cancer chemotherapies, especially the immune checkpoint inhibitors that we will talk about. That's emerging to be a very important area of discussion.

There's also much better understanding of what the diseases are, how we should be classifying them, and how should we be treating them. But even more importantly, I think there is an immense need to cross collaborate—working with rheumatology, working with dermatology, working with pulmonary—and one of the things that I would emphasize is there is a huge benefit in doing collaborative clinics or multidisciplinary clinics with rheumatology and other specialties. We do it here at Irvine. I know Hopkins does it, and the other centers may be doing it. I think it really adds value to the care of the patient.

NeurologyLive^®: Is there a chance for some of those opportunities to kick off at the MDA Clinical and Scientific Conference, with some many stakeholders in the room together?

Tahseen Mozaffar, MD: Absolutely. One of the beauties of the MDA conference, and the newer format that MDA has adopted over the last few years, is a very collaborative cross discussion. You bring in scientists, you bring in clinicians, and they spend 3 days together and talk about things. We have junior folks that are learning from this experience. There are talks on basic immunology, and they are immunologists and geneticists there.

Even for our session, we've invited rheumatology folks—Eleni Tiniakou, MD, who was coming from Hopkins is a rheumatologist as well. We have people who focus primarily on muscle pathology, I and Suur Biliciler, MD, do a lot of muscle pathology as well. I think we can learn from each other, and we can improve the care of the patient by essentially listening to each other and adopting the best care.

Angela Lek, PhD: We're hoping to get the word out that we are having this session specifically on myositis, so that we can begin to have productive dialogues between the Muscular Dystrophy Association and other like-minded folks in the field, on how we can work together and how we can collaborate, with the scientists as well as the clinicians, to advance the field of myositis as a whole.

NeurologyLive^®: What's the main unmet need when it comes to treating patients or educating providers on how to care for this group of individuals?

Tahseen Mozaffar, MD: I would say that a majority of the neurologists are not as familiar with the recent advances in myositis, and the improvement in terms of the disease classification systems, and the importance of antibody testing to further diagnose and stratified diseases. Antibodies can also be used to prognosticate disease, it predicts complications. There also needs to be a better understanding of the pathogenetic mechanisms, so the role of alpha interferon in dermatomyositis, the role in inclusion body myositis of the inflammatory pathway, which was pretty much abandoned as a hypothesis but now has been researched as a primary pathology.

My job is to make sure that the audience understands that myositis has come a long way. It's not just polymyositis and dermatomyositis anymore—there are 5 different diseases, and probably a sixth that's emerging. But in inclusion body myositis, which is the most common acquired muscle disease in adults, there is a lot of advancement. There are now 2 clinical trials starting up. So having a better understanding of that, not only the disease and how to manage it, but then also where you can get input from.

Angela Lek, PhD: And from a research point of view, MDA would be interested in attracting more basic science researchers to look into the underlying disease mechanisms of myositis. It's a heterogeneous disease, so it's a little bit difficult to understand what exactly the underlying causes are—there can be several of them. It's not like your standard genetic disease where one gene mutation equals one disease pathology. Genetics certainly affects myositis, but I think it's not the main driver. Genetics play a role in susceptibility and maybe as a disease modifier, but it's not the main driver of the disease. We want to encourage scientists to work on identifying some of the causal factors, so we can work towards more specific therapies instead of generic immunosuppressants.

Tahseen Mozaffar, MD: Exactly. Even within, for instance, myositis, there are genetic underpinnings. But also, there are some of newer technologies, like RNA sequencing at a deeper level. Or, now there are imaging modalities where you can be where you can put up to 30 antibodies onto a slide and look at the interaction of different proteins. There is so much work that can be done in myositis. I know our group is doing it. I know some of the other folks in the country are doing it. But these obviously, are not cheap research projects, and there's funding requirements. I think MDA is willing to increase its portfolio in terms of research funding for myositis.

Angela Lek, PhD: We want to encourage more scientists to put in more grant applications to investigate myositis with some of these new experimental techniques and technologies that are available. Muscular Dystrophy Association offers numerous funding opportunities, from our basic research grants to trainee fellowships to clinical trial grants or infrastructure grants.

NeurologyLive^®: Are there any conversations or topics related to myositis that are important for attendees, particularly of this meeting, to focus in on or think about?

Tahseen Mozaffar, MD: The fastest growing population is the people above the age of 50 years old. If you look at the census data, that is an almost an exponential growth, and that's the group of people that also are susceptible to inclusion body myositis. Now, as people get old, and they have difficulty getting up from a chair, a lot of the times the primary care physicians will attribute it to aging-related muscle weakness. Whether you call it sarcopenia, whatever term you use. These patients essentially get ignored. I would bet you that a lot of these patients probably have underlying inclusion, body myositis, or some other form of muscle disease, and right now, they are not being evaluated for it. Especially if we have treatments available, there may be a value in there. There are newer techniques that you can use. Ultrasound is becoming very important in picking up muscle abnormalities. We are a big fan of MRIs to look at muscle abnormalities. Short of doing invasive technologies or techniques, we can use noninvasive techniques. It's an important point to bring up that as the population dynamics change, we have to think of these things as well.

Also, immune checkpoint inhibitors, which are a wonderful class of anticancer medications, and more and more companies—there are at least four or five every month that come up—have done a wonderful job of curing cancers or controlling cancers, but they have tremendous adverse effects. And one of the big adverse effects is myositis. More and more of these cases will show up, and I think the neurologists, in general, need to be aware of it, but also primary care physicians need to be aware of it.

Again, there's a challenge. This is a source of great frustration for me. If a patient comes in with muscle weakness, or let's say they are found to have abnormal liver enzymes—and there is no such thing as liver enzymes, because it could be coming from muscle—they get a liver workup or a liver biopsy before somebody even bothers to check their muscle inside. A lot of these patients go to a hepatologist before they are referred to rheumatology or neurology, and I think that's a bias that exists in our training system. That's a bias that exists in the medical system. And a lot of patients have treatment delayed because of this.

NeurologyLive^®: What should others be excited about heading into this meeting?

Angela Lek, PhD: Well, this year we have sort of a practical bent on most of the sessions of the conference. We're going to talk about practical considerations in gene therapy—it's gained a lot of traction in the neuromuscular disease field, so how do we implement that? What are the safety considerations, what are the remaining hurdles? We're getting in experts from all over the world to pitch in on that session.

We also have a whole track dedicated to ALS, and all the latest advancements from academia from industry. And we’re bringing together all our ALS nonprofit partners in one room, and really hash out what are the priorities? How can we work together? That's going to be exciting.

We also have a session on translation of gene editing technologies. They work really well in the lab, but what is the potential so far that we see of gene editing technologies being translatable towards neuromuscular diseases in the clinic? There's also a session that I'm organizing on nonviral delivery technologies because those are starting to gain traction. As you know, AV based gene therapy has a lot of limitations in terms of the payload you can carry, and also a lot of safety considerations. We think that it's important to highlight other approaches to gene therapy that that that people are starting to look into. And then there is also a focus on ultra-rare neuromuscular diseases.

Tahseen Mozaffar, MD: One of the big areas of movement in neuromuscular disease is treatment of rare and ultra-rare diseases—especially with gene therapy but also with newer cutting-edge therapies, such as mRNA-based therapies. We are even doing CAR T-cell therapies in neuromuscular disorders. Learning more about it, and interacting with some of the researchers is going to be important.

One thing that I really like about the MDA is the opportunity for junior faculty and trainees to network and interact with some of the established folks, and I look forward to meeting more people and interacting.

Transcript edited for clarity. View the full agenda for the MDA 2023 Clinical & Scientific Conference here.

REFERENCE
FDA's Peter Marks, MD, PhD, to deliver Keynote Address at 2023 Muscular Dystrophy Association Clinical & Scientific Conference. news release. MDA. January 10, 2023. Accessed January 10, 2023. https://www.mda.org/press-releases/fdas-peter-marks-md-phd-to-deliver-keynote-address-at-2023-mda-clinical-and-scientific-conference