Fatigue and the missing enzyme

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Fatigue and the missing enzyme

Postby cheerleader » Mon Dec 01, 2008 12:23 pm

Researchers at Howard Hughes Medical Institute find an enzyme, neuronal nitric oxide synthase, is missing in mice with fatigue...after giving a vasodilator (viagra, in this instance) the mice are much more active and fatigue less easily. Here is the nitric oxide link we've been writing about in our vascular discussions, and provides an explanation for why many are finding relief from fatigue by pursuing this route.

In studies with genetically engineered mice that showed this form of fatigue after mild exercise, the researchers found that an enzyme called neuronal nitric oxide synthase (nNOS) is not present at its normal location in the membrane surrounding muscle cells. This means the blood vessels that supply active muscles do not relax normally and the animals experience fatigue after very mild exercise.

Howard Hughes Medical Institute researcher Kevin P. Campbell led a research team from the University of Iowa that reported its findings in the November 27, 2008, issue of the journal Nature.

In identifying the mechanism for this specific form of fatigue, the researchers found that the fatigue can be alleviated pharmacologically. When the scientists administered Viagra-like drugs to the mice with muscular dystrophy, they noticed an increase in their ability to move, as well as a dramatic increase in their activity after mild exercise. The treated mice were two to four times more active than untreated mice with muscular dystrophy. Prior to treatment, the same mice would become virtually inert after a short burst of low-intensity activity.

Nitric oxide signaling stimulates the generation of cGMP, a phosphodiester, which leads to a cascade of effects that culminates in the dilation of blood vessels. A phosphodiesterase (PDE) breaks down cGMP, limiting its duration to signal the vessels to dilate. Viagra enhances nitric oxide signaling by inhibiting the PDE from breaking down cGMP, allowing for prolonged vasodilation upon nitric oxide signaling. Further research involving longer-acting versions of PDE inhibitors could lead to the first therapies to improve the physical endurance of patients with muscular dystrophy and improve their quality of life, said Campbell. “Even with patients who have milder dystrophies, when they visit our lab and walk around for a short time become fatigued,” he said.

The provocative results might have implications for treatment of other conditions, such as multiple sclerosis, chronic fatigue syndrome, and even the aging-related muscle weakness that can lead to dangerous falls, Campbell speculated.


Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
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Postby yeb4432 » Sun Dec 07, 2008 8:10 pm

yes all of this is interesting. people with ms undoubtably have fatigue, but 97% i'd say is due to disrupted sleep. It is more complicated than it sounds; often times people with t he MS have spinalcord lesions that cause restless legs. even benign resless legs that you van feel can significantly disrupt sleep and make on exhausted. Other things include sleep hypoxia, and underlying cerebral demylinating focus causing arousal.

I'd check out a sleep study. I gaurentee you will be please in what you learn, especially how it relates to fatigue.
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