Erythropoietin in amyotrophic lateral sclerosis: A pilot, randomized,double-blind, placebo-controlled study of safety and tolerability

摘要

Preclinical studies demonstrated that erythropoietin is neuroprotective in different models of peripheral and central nervoussystem diseases. We investigated safety and tolerability of recombinant human erythropoietin (rhEPO) in amyotrophiclateral sclerosis (ALS). We performed a phase II double-blind, randomized, placebo-controlled study. After screening, 23patients were randomly assigned to rhEPO or placebo arm. Patients were examined during a six-month lead-in period, andthen they received fortnightly either 40,000 units of rhEPO or placebo for 24 months. Primary outcomes were adverseevents, safety, and death or tracheotomy. Treatment was safe and well tolerated. One patient in the rhEPO arm dropped outfor a superficial phlebitis. Median values of haematocrit, haemoglobin, red cells, and reticulocytes were non-significantlyhigher in rhEPO than placebo arm. Haemoglobin did not increase >1 g/d1 between subsequent doses. Anti-rhEPOantibodies were not detected. Survival and slope of ALSFRS-R curves did not significantly differ between treatment groups.RhEPO treatment was safe and well tolerated in ALS patients. Our results suggest that larger studies are warranted toconfirm safety of treatment and to investigate different dose schedule and efficacy.