Scientists discover clues to help children with rare muscle disease

Published in Annals Rheumatic Diseases, scientists closely analysed muscle samples from children with JDM and discovered the mitochondria, small energy-producing structures inside cells, were not functioning correctly.

It’s hoped this research will enable future treatments to be identified, especially for children who do not respond well to current treatment.

JDM is a rare condition that causes muscle weakness and skin rashes. It inflames the capillaries – the body’s tiny blood vessels – causing a rash on parts of the body like fingers and elbows. In some cases, the disease causes calcium deposits under the skin or deeper in tissues, which can restrict the movement of the joints.

JDM often also causes problems with muscles which can make everyday activities like walking or playing very difficult. JDM can also cause problems with other organs, like lungs or intestines, and in turn lead to organ damage.

JDM starts in two to four new cases per million children a year. However, this is incidence (new cases) - the actual prevalence of the disease is hard to estimate.

Researchers were able to closely analyse muscle samples from children with JDM and compare them to healthy muscles. They used a special new technology called spatial transcriptomics, which is like a super-powered microscope that can ‘see’ which genes are active in tiny parts of the muscle. This helped them understand what’s happening inside the muscles of children with JDM.

They identified two differences in the muscles of children with the condition. The first - mitochondrial dysfunction. Researchers found that the mitochondria in the cells of children with JDM were not functioning correctly – even in muscles that didn’t seem weak.

The second they found the body’s immune system goes into overdrive, through a process known as interferon activation. Essentially the immune system tries to fight off an infection that isn’t there, which can make children feel weak. While this process is already well known in JDM, this study was the first time it’s been mapped in such detail directly within the muscle.

Interestingly, the scientists found that these two problems don’t always happen together.

Professor Lucy Wedderburn, Consultant of Paediatric Rheumatology at GOSH and UCL Great Ormond Street Institute of Child Health, and co-senior author on the paper, said: “While more research into JDM is needed, this is a big step forward. It shows that looking at tiny details in muscle tissue can reveal important clues - and might help us find better ways to treat JDM in the future, for example by focusing on fixing the mitochondria, not just calming the immune system. This is an important finding as current treatments mostly focus on reducing inflammation.”

Five-year-old twin Lucia, from Twickenham in south-west London, was diagnosed with JDM in August 2024. However, her identical twin sister Isabella does not have the condition.

Lucia’s parents William and Caitriona noticed something wasn’t quite right when she had a red rash on the joints on her fingers and toes during a trip to New Zealand in Christmas 2023.

They thought it might be related to cold weather but when it got worse despite the warm weather, they began to grow concerned.

On returning to the UK, they went to see their GP and began a process of seeing several specialists until they were seen by now retired GOSH doctor Clarissa Pilkington who had set up a specialist unit for conditions like JDM at the hospital.

Lucia was diagnosed with JDM and started on two treatments in August 2024, a steroid and an immune-suppressing treatment called methotrexate.

Dad William Magee, a management consultant, said: “We were pleased to have an early diagnosis which was crucial to Lucia starting treatment quickly. However, the steroids weren’t as effective as hoped so Lucia was moved onto intravenous immunoglobulin which involves being admitted to hospital for two days each month for a transfusion of antibodies to boost her immune system.

“This research suggesting the link to mitochondria is so important because it opens the doors to a whole new type of treatment.

“It’s very reassuring to know that it could lead treatments which address the underlying causes, not just the symptoms of the disease – it is common for children with JDM to going into remission then have flare-ups in the future.

“We’d like Lucia and children with this condition to spend as little time as possible in hospital, so any research which leads to potentially more effective treatments can only be a good thing.”

He praised the skill of the GOSH clinicians, adding the treatment Lucia had received had been excellent. He said: “We were lucky – the doctors caught Lucia’s condition early. Not everyone with this condition is so fortunate.”

Dr Merry Wilkinson, senior research fellow at UCL Great Ormond Street Institute of Child Health and study co-lead, said: “This new and exciting research has shown us that there are mitochondrial problems in the muscle of JDM patients. We now need to investigate in the lab the use of existing drugs or developing new ones to improve mitochondrial health in JDM. There is a dire need for better treatments with less side effects and hopefully this research will start to address this problem.

“We are extremely privileged to work on the Juvenile Dermatomyositis Cohort and Biobank study, one of the largest databases of both clinical and biological JDM samples in the world, and very grateful to all the patients and families who donate samples to research like ours.”

Patients and families were involved at every stage of this research, including study conception, delivery and analysis through patient and public involvement and engagement group.

The study was funded by Versus Arthritis, Myositis UK, Great Ormond Street Hospital Charity, The Lorna and Yuti Chernajovsky Biomedical Research Foundation, George Bessell Trust and the National Institute for Health and Care Research GOSH Biomedical Research Centre.