Effect of dantrolene in Duchenne muscular dystrophy.

We have demonstrated that maneuvers capable of reducing Ca influx into cells have beneficial effects in dystrophic hamsters and Duchenne muscular dystrophy. Since dantrolene inhibits Ca release from the sarcoplasmic reticulum, its effects on DMD was studied in 7 patients of 6 to 13 years of age (mean 10.8 years). Patients were studied for 4 years with tri-monthly evaluations of manual muscle testing (MMT), functional activity, and serum CK and aldolase. During the first 2-year period, no medicines were given and served as control. In the second 2-year period, dantrolene 8 mg/kg/d was administered. No side effects were observed. In 1 patient, mild weakness occurred that disappeared when the dose was reduced to 6 mg/kg/d. The 95% confidence limit for the difference in slopes of regression lines from tri-monthly MMT was asymmetric in favor of dantrolene in 5 of 7 patients. Serum CK did not differ between the first and second year of the control and treatment periods, respectively. However, it fell significantly from the second year of control to the first year of treatment (P = 0.003). The fall during the first year of treatment was significantly greater (P less than 0.01) than in age-matched natural history controls during the same length of observation. There was a 3-fold reduction in CK when the pooled values of the first and second year control vs. treatment periods were analyzed. No changes were observed in functional activity and serum aldolase. The data suggest that dantrolene reduces serum CK in DMD associated with a lessening trend in MMT deterioration.