Challenges and Opportunities in the Treatment of Neuromuscular Disease in the Age of Therapies

Challenges and Opportunities in the Treatment of Neuromuscular Disease in the Age of Therapies

The fast-paced development and approval of therapies for the treatment of neuromuscular diseases (NMDs) have reshaped the landscape of neuromuscular health care over the past decade. Experts in precision medicine, health care systems, drug development, and patient care discussed the challenges and opportunities associated with novel therapies, as well as the need for collaboration and personalized care, in a general session at the 2024 Muscular Dystrophy Association (MDA) Clinical and Scientific Conference in Orlando, Florida.

Over the past 10 years, the U.S. Food and Drug Administration has approved an unprecedented number of therapies for NMDs, ushering in the age of therapies. The approval of gene therapies for various NMDs has traced a regulatory path for the development of interventions that target specific gene mutations. “We can envision a world a few years away where, at some point, we wouldn’t be developing individual treatments for individual diseases but we would be thinking more of interventional genomics,” said PJ Brooks, PhD, Deputy Director of the Division of Rare Diseases Research Innovation at the National Center for Advancing Translational Sciences. The development of survival motor neuron-targeted therapies for the treatment of spinal muscular atrophy and the successful use of combination therapies in this patient population may serve as a launch pad for therapies directed at other gene mutations, the speakers noted.

“We hear from patients regarding living with urgency,” said Barry Byrne, MD, PhD, Associate Chair of Pediatrics and Director of the Powell Gene Therapy Center at the University of Florida. “Their time frame is impacted significantly by their disease. In our work with Duchenne [muscular dystrophy], we see the clinical benefits that the patients experience, we see the opportunity for boys with Duchenne to be children, and play, and run. That is something [these patients] often are deprived of and now [they are] starting to regain those functions, and they can live their best life as children.”  

The approval of the first gene therapy for children with Duchenne muscular dystrophy in 2023 marked a major milestone in the treatment of this condition. “We have technology advancements and we have to start thinking about individualized therapies,” said Elizabeth McNally, MD, PhD, Professor at the Northwestern University Feinberg School of Medicine, Chicago. “These tools are in front of us right now. We have the ability to change genomes, we have the ability to develop reliable cell-based models for any one of these diseases, to test the therapy and show that it is efficacious, and then to be able to deliver it. We see what the steps are, now we have to [take them].”

Base-editing systems, which are constantly being updated and improved, have the potential to provide therapeutic platforms for many monogenic diseases, Brooks remarked. However, there are still many obstacles and challenges to delivering these therapies and making a significant impact on patients’ lives. The registry of NMDs includes more than 300 neuromuscular conditions that are extremely rare, affecting less than 1,000 individuals in the United States. “We can design therapies for almost any monogenic disease,” Brooks said. “The challenges are the delivery [of the therapies] and the regulatory path. I would like to see that [evolve] from drug development to the practice of medicine.” The main regulatory obstacles arise from a lack of biomarkers and functional scales for rare diseases. Developing a successful functional scale and correlating it with a biomarker is a challenging process that involves the collection of natural history data over time.

Large patient registries could provide the long-term data needed for the measurement of clinical endpoints, and may also be used to promote drug development that could benefit these patient populations, said Justin Moy, a patient advocate who is pursuing a PhD degree in biokinetics at Boston University. Moreover, patient-reported outcomes that reflect improvement or decline over time should be placed at the center of research.

In addition to regulatory hurdles, challenges to receiving adequate care include the transition from pediatric to adult neuromuscular health care, a lack of legislative uniformity between different states, and the coordination of care. When it comes to integrating research and health care, the United States is currently lagging behind other wealthy nations, Brooks noted.

Keeping the patients at the center of this journey and providing them with tools and resources such as patient navigation materials may help them overcome some of the obstacles they encounter in the health care system, the speakers said. “As we move into this new era of gene therapy, we also have to raise the educational level of patients and [family members], so that they know that, when these opportunities arise, they can take advantage of them, so that everybody can benefit from this new age [of therapies],” Moy added.

Widespread genome-based newborn screening may also unlock the potential of therapies to treat individuals before they become symptomatic, ensuring that they achieve the best possible outcomes, the speakers concluded.