Muscular Dystrophy Therapy

By , MD, PhD

Muscular dystrophy is a term which comprises a diverse group of genetic disorders that cause weakness and degeneration of skeletal muscle due to defective proteins critical for muscle structure and function. As muscle weakness usually progresses over time, lifestyle changes, assistive devices and occupational therapy are often required in order to help a person adapt to new situations.

Finding effective treatments for muscular dystrophies has proven demanding, in part due to their heterogeneity. Current treatments are based on palliation and primarily target the inflammatory response. Cell therapy has the potential to substitute damaged tissue by fusion of healthy cells with damaged muscle fibers, while reestablishing the adult stem cell pool for long-term muscle maintenance.

Conservative management

Physiotherapy to promote walking and prevent joint deformities is recommended in all cases of muscular dystrophies. A physical therapy program that includes passive stretching should be introduced early in the disease, right after establishing a diagnosis. Knee-ankle-foot orthoses at bedtime is often used to prevent contractures.

Individuals with certain types of muscular dystrophy have difficulties swallowing food as the condition progresses. As this can increase the risk of choking or developing aspiration pneumonia, consistency of food should be monitored, and exercises should be performed to improve the function of swallowing. In certain cases surgery can be pursued to treat this problem.

Currently, corticosteroids are the only class of drug that has been extensively studied in Duchenne muscular dystrophy and other types of the disease. Although experts used to suggest discontinuation of steroids when the patient starts to use the wheelchair full time, many affected individuals are continuing with its use indefinitely, hoping that it will provide benefit to respiratory musculature.

Nutritional therapies can also represent an appropriate and simple palliative approach. For example, treatment with the amino acids glutamine and arginine with added deflazacort were reported to improve nitrogen retention and maintain protein balance in patients with Duchenne muscular dystrophy. Leucine has also shown promise as an effective nutritional therapy for various types of muscular dystrophies.

Both recognition and treatment of cardiac manifestations of these conditions are increasingly important. The detection of arrhythmia and asymptomatic left ventricular dysfunction allows early and potentially life-saving treatment. In some cases of myotonic or Emery-Dreifuss muscular dystrophy, a pacemaker is often installed to correct an irregular heartbeat.

Therapeutic advances

Several promising experimental strategies for the treatment of muscular dystrophies are currently under investigation – most notably gene therapy aiming at reintroducing a functional recombinant version of the affected genes employing viral vectors, as well as modification of the dystrophin pre-mRNA, commonly referred to as exon skipping.

Three types of viral vectors have been used for the study of the muscular dystrophies: adenoviral, adeno-associated viral and lentiviral vectors. All three of them have shown certain success in transduction and stable expression of striated muscles; nevertheless, only adeno-associated virus vectors are now being used in clinical trials.

A number of different types of stem cells may be used in different ways to develop treatments for muscular dystrophy. The main stem-cell-based approaches currently being investigated are the production of healthy muscle fibers and significant reduction of inflammation. Still, methods to mitigate the host immune response to donor cells need to be sophisticated, and large-scale production of these cells needs to be established.

In conclusion, all aforementioned novel strategies face important challenges, imposed by the nature of muscular dystrophies such as the necessity to target different muscles in the body (including respiratory and cardiac muscles), the need for establishing long-term effect, the problem of fibrosis and the potential of unsolicited immune response. Albeit promising, much more research is necessary.

Further Reading

Last Updated: Feb 23, 2015

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