OP-01 - Treatment of sarcopenia by targeting Akt and muscle specific ubiquitin ligases. Evidence from mice and from a clinical trial

Abstract

Disuse muscle wasting may take place as a result of several such as joint immobilization, inactivity or bed rest. There are no good therapies to treat it. Allopurinol, a drug commonly used to treat hyperuricemia and gout, protects muscle damage, specially after exhaustive exercise and results in functional gains in old persons. Thus, we tested its effect in the prevention of atrophy of the soleus muscle after two weeks of hindlimb unloading in experimental animals (mice), and lower leg immobilization following ankle sprain in humans (Registration of the clinical Trial: EUDRACT2011-003541-17). We have found show that allopurinol protects against muscle atrophy in both mice and humans. The protective effect of allopurinol is similar, or even superior, to that of resistance exercise which is the best-known way to prevent muscle mass loss in disuse human models. We have also found that allopurinol protects against muscle mass loss by inhibiting the expression of ubiquitin ligases. Thus, the ubiquitin-proteasome pathway is an adequate therapeutic target to inhibit muscle wasting and underpins the role of allopurinol as a non-hormonal intervention to treat disuse muscle atrophy.