title: Erythropoietin in amyotrophic lateral sclerosis: a pilot, randomized, double-blind, placebo-controlled study of safety and tolerability.
abstract: Preclinical studies demonstrated that erythropoietin is neuroprotective in different models of peripheral and central nervous system diseases. We investigated safety and tolerability of recombinant human erythropoietin (rhEPO) in amyotrophic lateral sclerosis (ALS). We performed a phase II double-blind, randomized, placebo-controlled study. After screening, 23 patients were randomly assigned to rhEPO or placebo arm. Patients were examined during a six-month lead-in period, and then they received fortnightly either 40,000 units of rhEPO or placebo for 24 months. Primary outcomes were adverse events, safety, and death or tracheotomy. Treatment was safe and well tolerated. One patient in the rhEPO arm dropped out for a superficial phlebitis. Median values of haematocrit, haemoglobin, red cells, and reticulocytes were non-significantly higher in rhEPO than placebo arm. Haemoglobin did not increase >1 g/dl between subsequent doses. Anti-rhEPO antibodies 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 to confirm safety of treatment and to investigate different dose schedule and efficacy.
authors.affiliation: Neuromuscular Diseases Unit, IRCCS Foundation, National Neurological Institute Carlo Besta, Via Celoria 11, Milan, Italy. glauria@istituto-besta.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lauria
authors.forename: Angela
authors.initials: A
authors.lastname: Campanella
authors.forename: Graziella
authors.initials: G
authors.lastname: Filippini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Martini
authors.forename: Paola
authors.initials: P
authors.lastname: Penza
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Maggi
authors.forename: Carlo
authors.initials: C
authors.lastname: Antozzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Ciano
authors.forename: Pinuccia
authors.initials: P
authors.lastname: Beretta
authors.forename: Dario
authors.initials: D
authors.lastname: Caldiroli
authors.forename: Filippo
authors.initials: F
authors.lastname: Ghelma
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrara
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000818:Animals; D004311:Double-Blind Method; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos / Q000627:therapeutic use*; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; D004921:Erythropoietin