Brain Advance Access originally published online on August 29, 2007
Brain 2007 130(10):2577-2588; doi:10.1093/brain/awm203
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Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis
1Max Planck Institute of Experimental Medicine, Departments of 2Radiology and 3Clinical Neurophysiology, Georg-August-University and 4Hertie Institute of Multiple Sclerosis Research,Göttingen,Germany
Correspondence to: Prof. Hannelore Ehrenreich, MD, DVM, Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine, Hermann-Rein Strasse 3, 37075 Göttingen, Germany E-mail: ehrenreich{at}em.mpg.de
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.
Key Words: recombinant human erythropoietin; EPO; primary and secondary progressive multiple sclerosis; neuroprotection; neuroregeneration; neuropsychology; expanded disability status scale (EDSS); walking distance
Abbreviations: EDSS, expanded disability status scale; EPO, erythropoietin; MCV, Mean corpuscular volume; MCH, mean corpuscular haemoglobin; MEP, motor evoked potential; MRI, magnetic resonance imaging; MS, multiple sclerosis
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Received April 22, 2007. Revised July 9, 2007. Accepted July 31, 2007.
5 Present address: Department of Neurology, St. Josef-Hospital/Ruhr-University Bochum,Germany
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