Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis.
The neurodegenerative aspects of chronic progressive multiple sclerosis (MS) have received increasing attention in recent years, since anti-inflammatory and immunosuppressive treatment strategies have largely failed. However, successful neuroprotection and/or neuroregeneration in MS have not been demonstrated yet. Encouraged by the multifaceted neuroprotective effects of recombinant human erythropoietin (rhEPO) in experimental models, we performed an investigator-driven, exploratory open label study (phase I/IIa) in patients with chronic progressive MS. Main study objectives were (i) evaluating safety of long-term high-dose intravenous rhEPO treatment in MS, and (ii) collecting first evidence of potential efficacy on clinical outcome parameters. Eight MS patients, five randomly assigned to high-dose (48,000 IU), three to low-dose (8000 IU) rhEPO treatment, and, as disease controls, two drug-naïve Parkinson patients (receiving 48,000 IU) were followed over up to 48 weeks: A 6-week lead-in phase, a 12-week treatment phase with weekly EPO, another 12-week treatment phase with bi-weekly EPO, and a 24-week post-treatment phase. Clinical and electrophysiological improvement of motor function, reflected by a reduction in expanded disability status scale (EDSS), and of cognitive performance was found upon high-dose EPO treatment in MS patients, persisting for three to six months after cessation of EPO application. In contrast, low-dose EPO MS patients and drug-naïve Parkinson patients did not improve in any of the parameters tested. There were no adverse events, no safety concerns and a surprisingly low need of blood-lettings. This first pilot study demonstrates the necessity and feasibility of controlled trials using high-dose rhEPO in chronic progressive MS.
Ehrenreich
Hannelore
H
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Georg-August-University, Göttingen, Germany. ehrenreich@mpg.de
Fischer
Benjamin
B
Norra
Christine
C
Schellenberger
Felix
F
Stender
Nike
N
Stiefel
Michael
M
Sirén
Anna-Leena
AL
Paulus
Walter
W
Nave
Klaus-Armin
KA
Gold
Ralf
R
Bartels
Claudia
C
D000328:Adult; D000368:Aged; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019054:Evoked Potentials, Motor / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000187:drug effects; D011994:Recombinant Proteins; D016896:Treatment Outcome; D016138:Walking
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004921:Erythropoietin