Muscular dystrophy clinical trial results
What is the idea behind this study?
Muscular dystrophies are complex diseases that result from heritable defects in muscle proteins. This causes muscle fibre breakdown and weakness. In more severe cases, paralysis and death can result due to heart and breathing difficulties.
There are currently no therapies for muscular dystrophy that increase muscle strength, except for corticosteroids (prednisone/prednisolone, and deflazacort). Corticosteroids reduce muscle breakdown and increase repair of muscle tissue. Their anti-inflammatory effects reduce scar tissue formation. However, the benefits of corticosteroid therapy have only been well demonstrated in the short term. There are also side effects that limit their use, such as weight gain, changes in behaviour, and excessive hair growth.
Ibuprofen is an anti-inflammatory drug, and isosorbide dinitrate is a drug that delivers nitric oxide to muscle. Recent studies show these two drugs together are more beneficial for preserving muscle health in mice with muscular dystrophy than each drug alone, or without treatment. This combination therapy reduces muscle fibre breakdown, and increases the ability of the muscle to repair itself. Further, this therapy allows for muscle stem cell therapies to be more effective, by allowing muscle stem cells to find their way to the affected areas, and make new healthy muscle.
A first step to introducing this drug for treatment of muscular dystrophy in patients is to test its safety. This first clinical trial evaluates if there are severe side effects, and whether it is worthwhile to pursue this as a potential mode of therapy.
What did this study show?
A clinical trial was conducted on 71 patients; 35 were given the combination therapy, and 36 were untreated. All patients were at least 16 years old, and diagnosed with a form of muscular dystrophy.
All the patients were assessed by:
- Physical examination
- Neurological examination
- Muscle function
- Heart testing (e.g. echocardiography)
- Blood tests to monitor inflammation and muscle health
Patients were treated for 12 months, and were assessed again at 1, 3, 6, and 12 months. The information gathered was used to compare the health of the treated patients to those that were not, to see if there were safety concerns associated with the therapy.
There were no heart or lung problems and no safety concerns with blood pressure, or other specific tests of the blood. However, there was headache experienced in the first 7 to 10 days of treatment, temporary stomach pain, swelling of the lower legs, light-headedness, skin rash, and chest pain. One patient withdrew from the study due to a racing heart (increased heart rate), and two withdrew due to heart palpitations.
This clinical trial suggests that this combination therapy is suitable for a larger scale clinical trial to determine its benefit for people with muscular dystrophy.
What does this mean for patients?
Previous studies in the lab and in mice have shown that the combination of nitric oxide (delivered by isosorbide dinitrate) and an anti-inflammatory drug (ibuprofen) preserve muscle health in people with muscular dystrophy. Further, these benefits extend to preserving the function of the muscle to repair itself, and allow for muscle stem cell therapies to be more effective.
However, before this combination therapy can be made available to all people with muscular dystrophy, it must first pass clinical trials. This study is a small-scale clinical trial used to assess the safety of the therapy. This must be done before a larger scale clinical trial is conducted to show the therapy is beneficial for people with muscular dystrophy. Since it has now been shown the therapy is safe, the next step is to expand the trial to include a larger number of patients. The next trial will need to be more detailed to evaluate if it will be of benefit to patients. This process is underway, and may take several years before we know the answer.
Further information and links
The full research article from this study, in the research journal Pharmacological Research in 2012: Link to access the full article (cost): http://www.sciencedirect.com/science/article/pii/S1043661812000072
Previous studies demonstrating the effect of combined nitric oxide and ibuprofen therapy for muscular dystrophy:
Brunelli S et al. Nitric oxide release combined with nonsteroidal anti-inflammatory activity prevents muscular dystrophy pathology and enhances stem cell therapy.
Published in the Proceedings of the National Academy of Sciences USA, in 2007.
Link to access the full article (free): http://www.pnas.org/content/104/1/264.full.pdf
Sciorati C et al. Co-administration of ibuprofen and nitric oxide is an effective experimental therapy for muscular dystrophy, with immediate applicability to humans. Published in the British Journal of Pharmacology, in 2010.
Link to access the full article (free): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938824/
Sciorati C et al. A dual acting compound releasing nitric oxide (NO) and ibuprofen, NCX 320, shows significant therapeutic effects in a mouse model of muscular dystrophy. Published in 2011.
Link to access the full article (free): http://www.ncbi.nlm.nih.gov/pubmed/21609764
Muscular Dystrophy Campaign website: http://www.muscular-dystrophy.org/
Funding from the European Community’s Seventh Framework Programme project OPTISTEM supported this scientific work and summary. You can find out more about the scientists in this programme and the work they do at:
This summary was written by Long Nyugen