J Clin Neurol.  2014 Oct;10(4):342-347. 10.3988/jcn.2014.10.4.342.

Recombinant Human Erythropoietin in Amyotrophic Lateral Sclerosis: A Pilot Study of Safety and Feasibility

• Kim HY
• Moon C
• Kim KS
• Oh KW
• Oh SI
• Kim J
• Kim SH

• KMID: 2287514
• DOI: http://doi.org/10.3988/jcn.2014.10.4.342

Abstract

BACKGROUND AND PURPOSE
It has been shown that erythropoietin is neuroprotective in animal models of neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). The aim of this study was to determine the safety and feasibility of repetitive high-dose recombinant human erythropoietin (rhEPO) therapy in ALS patients.
METHODS
Two consecutive studies were conducted. We first recruited 26 subjects for an initial single-arm safety study. After a lead-in period of 3 months to assess the disease progression, rhEPO was infused intravenously (35,000 IU) once per month for 3 months, and the subjects were followed for an additional 3 months. The ALS Functional Rating Scale-Revised (ALSFRS-R) was used for clinical assessment. After confirming the safety of rhEPO, 60 subjects were recruited for the second controlled study (rhEPO and control groups), which involved a total of 6 infusions at a rate of 1/month.
RESULTS
There were no serious adverse events in the first study. The mean rate of decline in the ALSFRS-R score was lower during the treatment period than during the lead-in period (mean+/-SD: 2.6+/-1.8 and 3.7+/-2.6, respectively; p=0.02). However, the rate of decline during the subsequent 3 months returned to that observed in the lead-in period. In the second study, the mean rate of decline in ALSFRS-R score was significantly lower in the rhEPO group than in the control group (during months 0-3, 1.8+/-1.7 vs. 3.1+/-2.3, p=0.03; during months 4-6, 2.1+/-2.2 vs. 3.5+/-2.3, p=0.02).
CONCLUSIONS
Intravenous high-dose rhEPO is both safe and feasible for the treatment of ALS. Further investigation using different intervals and doses should be considered.

Keyword

amyotrophic lateral sclerosis; erythropoietin; pilot study

MeSH Terms

Amyotrophic Lateral Sclerosis*
Disease Progression
Erythropoietin*
Humans
Models, Animal
Neurodegenerative Diseases
Pilot Projects*
Erythropoietin

Figure

• 

  Fig. 1 Study timelines. Study I: a single-limb safety and efficacy study. Study II: a case-control extended study. : time to rhEPO injection, : time to clinical assessment, ▵: time to measure ALSFRS-R to evaluate primary outcome. ALSFRS-R: amyotrophic lateral sclerosis Functional Rating Scale-Revised, rhEPO: recombinant human erythropoietin.

• 

  Fig. 2 Efficacy assessment in studies I and II. A (study I): Comparison of the rates of decline (change in the ALSFRS-R scores over 3 months) during the lead-in (-3-0 months prior to 1 months), treatment (0-3 months), and follow-up (4-6 months) periods. During the treatment period, the rate of decline in the ALSFRS-R score decreased. B (study II): Comparison of the rates of decline in the ALSFRS-R scores in the controls and the rhEPO recipients. The mean rate of decline in the ALSFRS-R score was lower for the rhEPO recipients than for the controls. ALSFRS-R: amyotrophic lateral sclerosis Functional Rating Scale-Revised, rhEPO: recombinant human erythropoietin.

• 

  Fig. 3 Disease progression for 13 subjects as messured by ALSFRS. Of the 13 subjects, 7 displayed sufficient improvements in their functional abilities such that their scores were affected (A), whereas 6 subjects reported only minimal subjective changes that did not affect their scores (B).

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