DMD research

World Muscle Society 2021 – What we learnt

Duchenne UK’s Research Director, Alessandra Gaeta, attended the World Muscle Society (WMS) conference this September to learn about the latest research in neuromuscular diseases. WMS is an annual congress attended by top neuromuscular disorder research scientists around the world. 

This year’s conference included presentations on current DMD treatments in development and other areas of research in the DMD field, such as the development of more sensitive outcome measures to improve clinical trials.  

Three key take-home messages for the DMD community were: 

Clinical trial highlights 

During the conference, pharmaceutical companies shared updates from ongoing clinical trials for DMD treatments. These included updates from pharmaceutical companies Sarepta Therapeutics, Solid Biosciences and Capricor Therapeutics. 

Sarepta presented data from the following 2 trials. 

MOMENTUM, Part A; a clinical trial of an exon skipping treatment for boys who are amenable to exon 51 skipping.  

The study tested the impact of increasing doses in ambulatory patients. The biggest increase in exon skipping was shown with 30mg/kg dose after week 12, which correlated with a higher level of dystrophin production. Two serious safety concerns were reported, but both patients have recovered. Hypomagnesemia (low levels of magnesium in the blood) was observed in over 50% of patients on the higher dose, however this is manageable and can be monitored.  

Sarepta is now planning the Part B of the study, where ambulatory and non-ambulatory patients between ages 7 and 21 will be eligible. Read Sarepta’s press release here.   

SRP-9001-102; an ongoing clinical trial to evaluate the safety, efficacy and tolerability of Sarepta’s gene therapy treatment SRP-9001 in 4–7-year-olds.  

The study has led to some important findings and insights into clinical trial design and patient recruitment. SRP-9001-102 led to a high-level expression of dystrophin in the target muscle tissue; common side effects included vomiting, and four serious safety concerns were reported. Initial analysis of the study results showed that the drug effect was not significantly different in the treated patients when compared to placebo. However, when the patients were analysed based on their age groups, a statistically significant effect was detected in treated patients in the 4-5 age group. 

Solid Biosciences shared the data from their IGNITE DMD trial, which is testing their gene therapy treatment called SGT-001 

Results show evidence that the treatment is providing benefit on both functional and patient reported outcomes 12-24 months after their first dose.  The study did not include a placebo group, and trial participants’ functional motor abilities were compared to previously collected patient data. This showed that in patients treated with SGT-001, motor abilities declined less than what is typically expected in DMD natural disease progression without treatment. 

In addition, patients were able to maintain their 6-minute-walk distances over the trial period, whereas similarly-aged patients’ abilities would typically decline over this time. There were also no new safety findings from patients 3.5 years post-dosing. 

Read the full press release from Solid Biosciences here. 

CAPRICOR presented data from their HOPE 2 study  

This is a clinical trial of a type of cell and exosome-based therapy, called CAP-1002, which is designed to treat late stage DMD. The treatment aims to modify the immune system to encourage cellular regeneration. The results suggest that CAP-1002 is safe and effective at slowing muscle deterioration, with the potential to stabilise or reverse cardiac deterioration, while improving upper limb function. This is the first trial to use a new measure called PUL 2.0, which measures upper limb movement. It is better able to detect change over 12 months at all levels of ability. Currently, the trial is only available in the US.  

Read more about HOPE 2 here 

Natural History Study updates

Other interesting updates included an overview of a natural history study from by the Institut de Myologies in Paris and Great Ormond Street Hospital in London, presented by DMD Hub Research Physiotherapist Charlotte Lillien. The study was looking at the loss of upper limb movement over three years for patients with an exon 53 mutation and assessing the relationship between several measures of disease progression. 

The study included 40 boys (18 ambulatory and 22 non-ambulatory) and used a range of outcome measures collected every 6 months, comprising motor function measure (MFM), and used innovative devices to measure grip strength, pinch strength, and upper limb coordination.  

In addition, the study used MRI scans to measure level of fat in the muscles as a measure of fibrosis and muscle degeneration. The more fat is detected in the muscle, the more fibrosis is present and the less functional the muscle is. The outcomes measures changed over time and correlated with one another. This work is interesting as it could lead to novel outcome measures to assess treatment effects and benefit in the non-ambulant patients. 

Read the full publication here 

Highlights from Duchenne UK’s work 

Work that Duchenne UK has supported or funded was also showcased at the conference, including: 

Visit our research glossary for an explanation of the terms used in DMD research. 

Published on 18 October 2021

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