Significance of Creatine in Progressive Muscular Dystrophy,and Treatment of this Disease with Glycin

Abstract

Ever since Duchenne (de Boulogne) 1 made his classical studies of the progressive muscular atrophies the pathogenesis has been a subject of much contention. The view held by Duchenne 1 that the disease is primary in the muscles is supported by the clinical and pathological findings of many able workers, 2 , 3 but despite this, practically all methods of treatment have been based on the theory that the condition is secondary to some disturbance in the innervation. 4 , 5

Patients with this disease show a creatinuria even when maintained on a creatine-free diet, and in contradistinction to the normal subject excrete ingested creatine almost quantitatively (65-100%). This inability to retain ingested creatine is in proportion to the severity to the disease.

In our investigations on the origin of creatine, 6 many substances that could be considered biologically related to creatine were studied. We were able to confirm the findings of Gibson and Martin 7 who administered gelatin, and of Brand, Harris, Sandberg, and Ringer 8 who were the first to recognize the relationship of glycin, that the ingestion of this amino acid in these cases is followed by a large increase in the creatinuria. This significant relationship between glycin, a substance which the normal subject can readily synthesize, and creatine, which has been demonstrated to play an important role in.muscle function, suggested that the prolonged administration of this amino acid might have an influence on the clinical and chemical course of this disease. We have studied 6 patients during 8 experimental periods each of a few months' duration. Three of these patients had the clinical picture known as progressive muscular dystrophy, and 3 the symptom complex designated as pseudohypertrophic muscular atrophy. The daily ingestion of 5 gm. of glycin was followed by a definite rise in the creatinuria; 15-20 gm. increased the daily excretion of creatine 300-500 mg., the more advanced cases excreting the larger amounts.