The global search for new treatments: highlights from the Annual Congress of the World Muscle Society

22 November 2024

Each year the World Muscle Society brings together scientists and healthcare professionals from across the world to share the latest neuromuscular research. Our research manager John Copier attended the conference this year. It was a great networking opportunity, and he heard about lots of new and ongoing research developments. John shares an update about the conference.

The 29^th Annual Congress of the World Muscle Society ran from 8 to 12 October 2024, and much of the discussion focused on the development of potential treatments for muscle wasting and weakening conditions.

Can we target the immune system in muscle wasting and weakening conditions?

Many muscle wasting and weakening conditions are due to the immune system not working correctly. While the immune system plays a key role in keeping us healthy by producing antibodies to fight bacteria and viruses, in some diseases it can produce antibodies against its own cells. For example, in myasthenia gravis, the immune system produces antibodies which attack proteins that are vital for muscle movement. Some conference talks focused on the use of CAR T cells to treat muscle wasting and weakening conditions that involve the immune system. This is a treatment originally pioneered in cancer treatment, where cells of the immune system (specifically T cells) are altered so they can recognise and kill a target. Researchers have shown that CAR T cells can be used to remove the cells that produce the damaging antibodies in myasthenia gravis. Further research is now needed to continue the development of this potential treatment.

Researchers are also trying to use this approach to reduce immune responses. Immune responses are our body’s reaction to something from outside the body entering the body, to stop it from causing harm. To deliver gene therapy into the body a viral vector is sometimes used, and while these are harmless, they can produce a response in the immune system. Reducing this response could make it easier to deliver therapies.   

The challenges of gene therapy development

While great strides are being made in the development of gene therapies, there are still some challenges to overcome. Including, how gene therapy can be delivered into the body and how to specifically target muscles.

Professor Jeffery Chamberlin, Washington University, discussed how his team are trying to address some of these challenges for Duchenne muscular dystrophy (DMD). DMD is caused by a change in the dystrophin gene. This leads to a protein called dystrophin not working as it should, or not being produced at all. Dystrophin is important in maintaining the strength of muscles.

Researchers are trying to find ways to introduce a working version of the dystrophin gene into the body. However, the dystrophin gene is one of the largest genes in the body, which makes it difficult to be delivered into the body. The gene therapy delandistrogene moxeparvovec produces a smaller but functional version of dystrophin, yet these smaller versions generally don’t work as well as the full-sized version. Therefore, finding a way to introduce the full-sized version may be more beneficial for people with DMD.

One trick, developed in Professor Chamberlin’s lab, is to cut the dystrophin gene into smaller chunks. These small chunks are altered so they can link together inside a cell to make full-length dystrophin. So far, this approach has shown promise in models of DMD, but further research is needed to see if it could benefit people with DMD.

Finding new ways to determine if a treatment is working

With many potential new treatments in development, researchers need to make sure they can accurately determine if a treatment is working or not. Researchers are searching for markers within the body (called biomarkers) which can reliably do this. Dr Krista Vandenborne, University of Florida, talked about the use of magnetic resonance imaging (MRI) to see muscle changes in ambulant boys with DMD who are treated with delandistrogene moxeparvovec.

In people with DMD fat progressively replaces muscle over time, contributing to the weakening of the muscle. Fat and muscle can be seen on MRI scans, so using them could help to measure the changes in DMD. In a study of 39 people, less fat was seen in the muscle of those treated with delandistrogen moxeparvovec compared to those who received the placebo (dummy drug). This indicates disease progression was slower for those receiving delandistrogen moxeparvovec and that MRI use has the potential to monitor progression.

The importance of early intervention

Finding the best time to give people a treatment is also important. In some conditions, damage can happen inside the body before symptoms appear. Starting treatment as early as possible may be able to delay the onset of symptoms, but this still needs to be tested in a clinical trial.

Laurent Servais, University of Oxford, talked about Rainbowfish, a two-year study testing the safety of risdiplam and if it works in presymptomatic children with spinal muscular atrophy (SMA). These are children who have the gene change but were not yet showing symptoms. As the children had no symptoms at the start of the study, it was hard to measure if the treatment had an effect. However, they were able to see that those who received the treatment showed improvements in motor function compared to what would typically be expected. This trial provides evidence that earlier treatment with risdiplam may be beneficial.

We are already looking forward to the 30^th Annual Congress of the World Muscle Society and will continue to report back from conferences we attend. In the meantime, find out about the research we fund.