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Monday 8 December 2008

Research could explain exercise-induced fatigue for people with neuromuscular conditions

A recent study published by Professor Campbell and his colleagues at the University of Iowa showed that in mouse models, a chemical substance called neuronal nitric oxide synthase (nNOS) causes, at least in part, the fatigue experienced by people with neuromuscular conditions after exercise. The findings of this research could open up a new opportunity to treat excessive fatigue associated with mild exercise in many neuromuscular conditions.

Contents:

What does this new research show?

The researchers observed that in several mouse models of muscular dystrophy, nNOS was absent from its normal location at the membrane of muscle cells. Absence or mislocalisation of nNOS at the muscle membranes prevents relaxation of blood vessels which supply the muscles with oxygen. This lack of oxygen in muscle cells, in turn, might be one of the reasons why the animals experience extreme fatigue after mild exercise.

The paper states that approximately 60 percent of people with neuromuscular conditions show severe fatigue. Consequently, the researchers analysed muscle biopsies of patients with different myopathic conditions. They found that in most biopsies the amount of nNOS present at the membrane was also reduced or completely absent, indicating that the fatigue in humans may be caused by the same biological mechanism as that in the mouse.

The results of this research suggest that targeting nNOS, and the signalling pathway that it is part of, might help to treat extreme muscle fatigue. This could be achieved by using drugs which work by preventing constriction of blood vessels, such as Sildenafil.

What does this mean for people with muscular dystrophy?

These are very promising findings that could form the basis for treating the prolonged fatigue which occurs in people with neuromuscular disorders. The results of the experiments, carried out in mice, suggest that a drug called Sildenafil, also known as Viagra, could be considered as a potential treatment. However, it is important to remember that benefits seen in animals do not always translate into human medicine.

Although research in this area is positive, it is still in its very early days and we look forward to further research that will demonstrate the impact it might have for people with neuromuscular disorders.

Background information

Prolonged muscle tiredness which occurs after mild exercise in people with various forms of neuromuscular conditions can be caused by lack of nNOS- a chemical substance at the muscle membrane. This substance when present in normal muscles triggers various forms of chemical reactions in the muscles which eventually lead to dilation of blood vessels in order to increase blood flow into exercising muscles.

Viagra increases blood flow by preventing the action of an enzyme called Phosphodiesterase (PDE) which breaks down another substance - cyclic guanosine monophosphate (cGMP). Preventing the action of PDE causes relaxation of blood vessels which in turn leads to increased blood flow.

Further information and links

Click here for more information about muscular dystrophies.

Find out about Dystrophic hearts treated with viagra

The original paper is not freely available and is written in scientific language. The reference for the paper is:
Kobayashi YM, Rader EP, Crawford RW, Iyengar NK, Thedens DR, Faulkner JA, Parikh SV, Weiss RM, Chamberlain JS, Moore SA, Campbell KP. Sarcolemma-localized nNOS is required to maintain activity after mild exercise. Nature. 2008 Nov 27;456(7221):511-5.

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