EPO Protects from Mouse Multiple Sclerosis
New Jersey, USA -
There are many studies discuss immune modulation by stem cells by mechanisms such as IDO production, soluble HLA-G, and hepatocyte growth factor. An interesting question is whether stimulators of various stem cell activities may have immune modulatory activity as well. For example, we know that GM-CSF, a cytokine that stimulates production of granulocytes and macrophages can protect from autoimmune diabetes in the mouse. The study above describes erythropoietin as having immune modulatory activity.
The authors showed EPO:
1. Suppresses TNF-alpha production
2. Downregulates in vitro and in vivo antigen-specific recall responses to myelin oligodendrocyte protein (MOG) derived peptides
3. Inhibits EAE induction
4. Stimulates Treg (as detected by FoxP3 staining)
5 Inhibits Th17
Overcoming the hematopoietic effects by specific dosing or different forms of EPO will be necessary before using it as an immune modulator. However, this immune suppressive activity of IDO may have implications in patients with anemia of chronic disease that are taking EPO.
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Judashpriest said...
Already been tested in humans. Phase I/IIa study in Germany:
1: Brain. 2007 Oct;130(Pt 10):2577-88. Epub 2007 Aug 29. Links Exploring recombinant human erythropoietin in chronic progressive multiple sclerosis. Ehrenreich H, Fischer B, Norra C, Schellenberger F, Stender N, Stiefel M, Sirén AL, Paulus W, Nave KA, Gold R, Bartels C.Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Georg-August-University, Göttingen, Germany. ehrenreich@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.