Clinical trials of allopurinol in Duchenne muscular dystrophy.

A wide range of different disturbances characteristic of Duchenne muscular dystrophy (DMD) can be attributed to a fundamental chronic shortage of intracellular adenosine 5'-triphosphate (ATP), in turn arising from a basic lack of total adenylate. Purine conservation by the hypoxanthine isomer allopurinol, which promotes salvage and inhibits catabolism, greatly increases muscle ATP and total adenylate, with corresponding clinical benefit. Among subsequent confirmatory clinical trials some gave positive results, while others provided no information. Reasons given why these latter proved uninformative include asking questions either irrelevant and/or incapable of being answered, not least in older boys with too much shrinking fibrous tissue infiltrating too little remaining muscle. Informative results from any metabolic intervention can be expected only where sufficient muscle is left to respond, and this age-linked effect is everywhere evident in the positive trials. Thus, if an effect of allopurinol now seems apparent, and since it is extremely safe and does not enter the genetic material, it is suggested that it be administered shortly after birth before irreversible pathological changes occur. This implies neo-natal male mass screening, easily accomplished by a simple dried-blood spot test, and already carried out successfully elsewhere.