Gene Therapy Research

Gene therapy research and development has grown exponentially in the last decade and there are now therapies (both approved and in development) for previously untreatable neuromuscular conditions.

Gene therapies can work by several mechanisms:

• Adding a functional copy of a disease-causing gene (gene addition).
• Inactivating gene expression for a disease-causing gene that produces toxic proteins or transcripts.
• Editing a disease-causing gene so it can produce a (partially) functional protein.

Genetic neuromuscular diseases are often caused by the lack of a protein; gene therapy provides a functional gene copy to muscle or motor neurons resulting in production of the missing protein. In gene therapies for neuromuscular disease, genes are delivered via a viral vector to target skeletal muscle and heart.

Due to the progressive nature of neuromuscular disease, the timing of gene therapy is incredibly important as the restoration of missing protein will not restore tissue and function that is already lost. Clinical research suggests that the earlier the treatment is received, the more therapeutic impact it will have.

In recent years, the neuromuscular community has seen several products advance in clinical development and there are already two approved gene therapies for medical use:

• ZOLGENSMA® (Onasemnogene abeparvovec) used as a therapeutic option for the treatment of Spinal muscular atrophy (Type I). It involves AAV9 viral vectors that deliver a copy of the genetic code of the SMN gene, which is mutated in SMA patients.
• ELEVYDIS (Delandistrogene moxeparvovec) only approved in the USA, Elevydis is used as a therapeutic option for the treatment of ambulatory paediatric patients aged between 4 and 5 years old and diagnosed with Duchenne muscular dystrophy. Elevydis involves AAV74 viral vectors that deliver a copy of the genetic code for a micro-dystrophin. The code for full-length dystrophin, which is missing in Duchenne patients, is too large for AAV viral vectors. Patients who have a deletion that involves exon 8 or 9 are excluded from treatment due to the risk of an auto-immune response to the micro-dystrophin

There are other gene addition therapies currently in clinical development for Duchenne muscular dystrophy, X-linked myotubular myopathy, Pompe disease and Limb-girdle muscular dystrophy.

In parallel, gene editing approaches are in preclinical development for many neuromuscular diseases. This involves the CRISPR/Cas system that can be utilized to correct small mistakes, or to induce mistakes to, for example, prevent production of gene transcripts that are toxic or code for toxic proteins.

As part of our Education Programme, TREAT-NMD hosted an Expert Gene Therapy Masterclass (held in Amsterdam in May 2023) and, in March, partnered with the Muscular Dystrophy Association at the 2023 MDA Conference as part of the Practical Considerations in Gene Therapy Track.  Both CME accredited events were a huge success; health care professionals and allied care providers were able to learn about the latest developments in gene therapy for neuromuscular diseases to deliver the best care and treatments for patients.

We have education events focused on the latest in gene therapy planned for 2024 – sign up to our newsletter and follow us on social media to be notified when details of these events are released.