Each year, the World Muscle Society (WMS) Annual Congress brings together the best minds in neuromuscular research, clinical care, patient advocacy, and industry. It offers a dynamic platform for sharing new data, fostering collaborations, and advancing the science behind therapies for diseases like Duchenne muscular dystrophy. This year’s event in Prague, Czech Republic, featured talks focusing on developments in gene therapy, clinical trial updates, and insights from across the field. Below are highlights from the 2024 meeting:

Victor Dubowitz Lecture: Gene Therapy in Duchenne

Presented by Jeffrey Chamberlain, PhD, University of Seattle

Dr. Jeffrey Chamberlain delivered this year’s prestigious Victor Dubowitz Lecture. During this lecture, Dr. Chamberlain discussed the history of the development of gene therapy in Duchenne including the discovery of the DMD gene and muscle promoter elements to drive expression of proteins in specific tissues, experiments exploring the limits of what could be removed from the DMD gene to retain a functional protein, the initial discoveries that adeno-associated virus (AAV) injection could lead to persistent expression of a transgene  and how we arrived at our current landscape of microdystrophin gene therapies.

Dr. Chamberlain also presented advancements in science that could shape the future of  gene therapy, highlighting some of the work pursued in his lab. Chamberlain addressed the main components of gene therapies, which includes the vector for delivery and the microdystrophin transgene, and how these can be improved Researchers have been working to modify vectors  to  enhance targeting of muscle tissue, which could facilitate lower doses of virus with sustained or improved delivery to muscles.

Dr. Chamberlain presented work out of his lab that is exploring the delivery of larger dystrophin proteins, both midi-dystrophins and even full length dystrophin. These new systems use two or three muscle-specific viruses to deliver multiple sequences of dystrophin protein that can be combined in the cell to create the larger dystrophin proteins. In aged preclinical models, researchers are able to get expression of these larger proteins that may confer more benefit than microdystrophin constructs. It is still early days for these experiments, and work needs to be done to ensure these approaches can be safely translated to humans, but it provided an exciting look into the continued development of gene therapy for Duchenne.

Industry Symposium

As part of the Congress, industry partners sponsor symposia for the researchers and clinicians. Tese sessions often have a range of educational materials presented for discussion. The symposia this year, presented by Dyne, Edgewise, Italfarmaco, and Pfizer, covered topics including:

• The current and ongoing studies collecting Becker natural history data and how that impacts clinical trial design. 
• Exploration of functional outcome measures and the heterogeneity of Duchenne, meaningfulness of those outcome measures, trial design challenges, and how novel outcomes could be more reliable measures of the benefits of drugs.
• Lessons from spinal muscular atrophy (SMA) that may be applicable to Duchenne when clinicians consider combination therapy. 
• The role and importance of newborn screening, highlighting parent views on newborn screening that PPMD collected and recently published. 

Short Oral Presentations

The majority of attendees to WMS present data, often in the form of poster presentations. For example, PPMD shared a poster exploring the consistency of functional outcome measures collected across the Certified Duchenne Care Centers and clinician barriers to capturing outcome data. A subset of those presenting posters are asked to participate in sessions where they present their data to a larger audience. A few of those short oral presentations are highlighted below:

• Dr. Glenn Walter – Presented initial data from the protein mapping project, which has identified proteins that may predict changes in disease milestones.
• Dr. Margaux Poleur – Discussed the usability of wearable devices with toddlers to capture 95% stride velocity, and how these devices enable reliable data capture on a young patient population where traditional functional outcome measures (e.g. NSAA) can be more difficult to capture.
• Dr. Luca Bello – Shared natural history data of Becker muscular dystrophy, focused on the longitudinal changes in motor function within this population.

Lecture Presentations

This series of educational talks focused on specific areas of interest within the WMSand highlighted data being generated across the field. Examples of some of the talks:

• Dr. Virginia Arechavala Gomeza presented an overview of precision medicine in neuromuscular diseases, sharing the methods, challenges, and potential improvements for the use of therapeutic interventions like exon skipping, gene replacement, or gene editing.
• Dr. Pietro Spitali gave an overview of the use of RNA sequencing and protein biomarkers. Dr. Spitali  presented rapidly evolving technologies allowing scientists to look at muscle tissue with high resolution for characterizing specific transcripts expressed in individual cells. This talk also explored how these methodologies may be used in clinical practice and drug development. 

Clinical Trial Updates

Sessions focused on covering updates from clinical trials across multiple neuromuscular diseases.

• Dr. Krista Vandenborne presented exploratory imaging data from Part 1 of the Phase 3 EMBARK study with SRP-9001 (ELEVIDYS), where patients were randomized to SRP-9001 or placebo. The study collected MRI data on patients aged 4-8 years old at baseline and 52 weeks. This was a substudy of patients involved in EMBARK and therefore was not powered for statistical significance. Dr. Vandenborne reported that the magnitude of change in fat fraction at week 52 was lower in treated patients compared to control. This data suggested stabilization or slower progression of muscle pathology with SRP-9001. It is important to note that as this was a small cohort size being evaluated there are limitations in the ability to apply statistical significance to these results. 
• Dr. Francesco Muntoni presented data from the Phase 3 CIFFREO study of fordadistrogene movaparvovec, Pfizer’s gene therapy product that was previously reported to have failed to meet its primary endpoint of change from baseline at week 52 in the NSAA. Dr. Muntoni also reported that there was no statistically significant difference between the placebo and treated patients in the secondary outcomes (such as 10M Walk/Run). Patients who received gene therapy did have robust expression and distribution of the modified dystrophin with an average dystrophin expression of 85% and 52% positive fibers.
  • While these results are disappointing, we are grateful that Pfizer has continued to share negative data with the community so we can learn from these results and build on these outcomes. We also want to acknowledge and thank the brave patients and families who participate in clinical trials, despite the absence of guaranteed benefit. Your contributions are invaluable in helping to bring therapies to all in our community.

Industry Announcements & New Data

When companies have new data, they often share those data for the first time at scientific conferences. Below you can find links to press releases from various companies who released new data at WMS 2024: 

• Capricor Therapeutics – Long-Term Data from HOPE-2 OLE Study of CAP-1002 in Duchenne
• Entrada Therapeutics – Additional Biomarker Data from ENTR-601-44 in Healthy Volunteers 
• Satellos – Four-Month Functional and Biomarker Data in Large Pre-Clinical Duchenne Model 

What is World Muscle Society?

WMS was started 23 years ago by neurologist Professor Victor Dubowitz. Dr. Dubowitz led the Great Ormond Street, London clinic for many years and was one of the first to clinically adopt the use of steroids in Duchenne. Dr. Dubowitz believes it is important for all individuals in the field to meet face-to-face to discuss opportunities, establish collaborations, and to connect at a forum showcasing findings, new investigators, and new knowledge. To that end, WMS and Dr. Dubowitz’s journal, Neuromuscular Disorders, have grown to become incredibly important for the neuromuscular disease community. From relatively few investigators coming together to today, where over 750 people (bench scientists, young investigators, clinicians, companies, advocacy organizations, and investors) come together in different locations around the world, committed to driving therapies for neuromuscular diseases.