Recombinant Human Erythropoietin Therapy in Amyotrophic Lateral Sclerosis Patients

Abstract

Background & Objectives: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative condition characterized by loss of upper and lower motor neurons in the brain and spinal cord. In spite of numerous researches, riluzole remains the only effective therapy, but with only minimal effects on survival. In previous reports, erythropoietin (EPO) has shown the neuroprotective effects, including anti-apoptotic and anti-inflammatory actions on central nervous system in vivo as well as in vitro. Therefore, we conducted a preliminary study to evaluate the effect of EPO on the modification of disease progression and to ascertain most appropriate candidates for EPO therapy.

Method: Fifty-seven patients with probable and definite ALS on the basis of El Escoreial criteria were recruited for this study. After the lead-in period for 3 months to assess the progression of disease, recombinant human erythropoietin (rhEPO) was injected intravenously (35,000 IU/30 min/50 ml) four times at an interval of 1 month (0, +1, +2, +3 month) to rhEPO group. Patients were monitored by clinical evaluation including ALS functional rating scale-Revised (ALSFRS-R), subjective symptoms and signs by 6 months follow up period. As a primary outcome measure, the change of ALSFRS-R score was compared between rhEPO (n=21) and control (n=20) groups. Additionally, the demographic and clinical characteristics in patients showing beneficial effects on EPO therapy were evaluated as a secondary outcome analysis. To assess the safety, patients were closely monitored for adverse events including thrombocytosis, malignant hypertension, and myocardial ischemia. Besides hemodynamic monitoring, each patient had complete blood cell count, blood urea nitrogen, creatinine, electrolytes, glucose and liver enzyme.

Results: When compared with control group, the rhEPO treatment could reduce the change of ALSFRS-R during 1st half follow up period. In addition, these disease modifying effects were enough to improve the functional deficits during 2 to 3 weeks after each rhEPO injection in 10 patients and more prominent in patients with short duration and rapid progression among the rhEPO group. The intravenous administration of rhEPO also had modest but significant beneficial effects including improvement of muscle power, decreased drooling, mood stabilization, and decreased spasticity. No significant adverse effects were noted. The hematocrit, hemoglobin, red blood cell counts, liver enzyme, and blood pressure remained stable.

Conclusion: Intravenous rhEPO in ALS is both safe and well tolerated. Moreover, this approach may be worthy of further investigation with various treatment interval and dosage.