We are very pleased to announce a 3 year grant award to Dr Jim Dowling and his team at Sick Kids Hospital, Toronto, Canada, to study Liver disease in X-Linked Myotubular Myopathy. This grant of £300,000 is awarded in partnership with Muscular Dystrophy UK, who are contributing £60,000 to the project.

We have seen in recent years that some individuals with x-linked myotubular myopathy have had liver problems. Liver complications have also had an impact on the progress of clinical trials. The grant to Dr Dowling and his team – the largest made in the Myotubular Trust history – is testament to the importance of this topic, and our commitment to helping the community of patients, researchers and medics to better understand how the liver works in myotubular myopathy.

Pictured, from left to right – Rebecca Simonian, Jim Dowling, Nesrin Sabha, Ashish Deshwar, Emanuela Pannia and Sophie Karolczak

Dr Dowling and his team’s important work explained:

XLMTM and liver disease

Over the past few years, it has become clear that some individuals with X-linked myotubular myopathy (XLMTM) can have problems with their liver. To improve the care of these patients, we need to understand how having a myotubular myopathy-causing genetic change can affect how the liver works, and responds to stress. A team at SickKids, led by Dr. Dowling, has already made great progress in understanding why this is, but more research is needed to help prevent these problems from happening.

Developing understanding

In their project, Professor Dowling’s team plans to use both mouse and human liver cell models to better understand the cause of liver disease in people living with XLMTM and to help develop a treatment.

The team has a mouse that has the same genetic change found in people with XLMTM and they’ve discovered that some of these mice also have liver problems. They have also found that different diets in these mice can either make the liver disease better or worse depending on the kind of diet. The team now plan to test out different formulas currently given to humans to see whether they have a positive or negative effect on the liver with the goal of identifying one that improves the liver symptoms.

It also seems likely that there are potential triggers, such as infection, that can make liver problems in XLMTM more likely to occur, or more severe. While fortunately this has not led to significant liver diseases in most patients, understanding these risk factors and how they may impact disease and respond to new therapies, is critical. To address this challenge and better define the interplay between environment, therapy and XLMTM liver disease, they will study differing triggers using the XLMTM mouse model.

Building on research

Professor Dowling’s team has already created human liver cells with the myotubular myopathy mutation. Professor Dowling says “We plan to use these cells to research at the level of individual molecules why the genetic change in XLMTM is harmful to the liver, and why it differs between different people. Finally, we hope to use both this model and our mouse model together to then test out different drugs with a goal of identifying one that can improve the liver problems and that could be used to treat individuals with XLMTM.”

Thank you

This 2023 grant is only possible because of the fundraising of our families and supporters. Since founding in 2006, 100% of your fundraising has gone into promising research projects.

Myotubular Trust continues, year on year, to raise core administration costs separately, by applying to other charities, foundations, and specific sponsors. This enables every single penny that you donate to make a difference to our scientific understanding, and the development of potential therapy routes for our group of conditions.

Thank you