Quantitative assessment of sustained-release 4-aminopyridine for symptomatic treatment of multiple sclerosis.

OBJECTIVE

To evaluate the efficacy of 4-aminopyridine sustained release (4AP SR) (fampridine, EL-970) using quantitative measures of motor function in multiple sclerosis (MS) patients.

BACKGROUND

In vitro, 4AP improves conduction through demyelinated axons. A previous multicenter trial of 4AP SR using the Expanded Disability Status Scale (EDSS) as the primary outcome was unable to establish clinical efficacy.

DESIGN/METHODS: Ten MS patients with stable motor deficits (EDSS 6.0-7.5) were given 4AP SR 17.5 mg bid and placebo for 1 week each in a double-blind, placebo-controlled, crossover trial. Time to walk 8 meters, time to climb four stairs, maximum voluntary isometric contraction measured quantitatively (MVICT), manual muscle testing (MMT), grip strength, EDSS, and the patient's global impression were measured.

RESULTS

Timed gait was improved on 4AP SR compared with placebo in 9 of 10 subjects (p = 0.02). Timed stair climbing, MVICT, MMT, grip strength, and EDSS showed nonsignificant improvements on 4AP SR. Based on their global impressions, seven subjects preferred 4AP SR over placebo; only one preferred placebo. There were no serious side effects.

CONCLUSION

4AP SR improved motor function in MS patients. The quantitative outcomes used in this study permit more sensitive evaluation of the therapeutic effect and promise to be useful in future trials of symptomatic treatments for MS.