McArdle’s disease is a common metabolic disorder characterized by
marked exercise intolerance, premature fatigue during exertion,
myalgia, and cramps. The pathophysiology involves a deficiency of
myophosphorylase enzyme resulting in an inability to degrade glycogen
stores. The insertion/deletion (I/D) trait in the angiotensin-
converting enzyme (ACE) has been suggested to be a strong modulator
of severity in McArdle's disease. Dr. Andrea Martinuzzi and
colleagues have previously observed that a common polymorphism
insertion/deletion (I/D) in the ACE gene is associated with disease
severity. The severity of symptoms may vary from case to case, and
this variability may be in relation to the activity levels of ACE,
with patients carrying one or two D alleles being the most severely
affected.
In the present collaborative study coordinated by Dr. Andrea
Martinuzzi, the authors hypothesized that modulating ACE activity
through the use of inhibitors may reproduce the condition of those
patients with a milder phenotype and may result in an alleviation of
the symptoms of the disease such as exercise intolerance. In this
double-blind, randomized, placebo-controlled clinical trial the
efficacy of the ACE inhibitor ramipril, a drug commonly used to treat
hypertension and congestive heart failure, was examined in 8 patients
with McArdle’s disease. This hypothesis is further supported by
studies showing that patients treated with ramipril for
cardiovascular problems had increased strength and resistance
exercise. Patients were evaluated in terms of their muscular strength
and their perceived quality of life. Besides the fact that ling-term
low treatment with low-dose ramipril is safe and well tolerated, this
study failed to show any treatment effect in the objective measures
of exercise performance and muscle metabolism.

Références : Muscle Nerve. 2007 Dec 20 [Epub ahead of print]