Erythropoietin
Erythropoietin (EPO) is a glycoprotein hormone that primarily controls red blood cell production. Interest in utilizing this pharmaceutical agent to treat acute SCI stems from one of its most commonly studied secondary functions, the prevention of neuronal apoptosis in the presence of ischemia (Siren et al. 2001). Even less well understood, EPO has been shown to elicit anti-inflammatory properties, minimize lipid peroxidation, scavenge free radicals, regenerate axons, and reduce calcium ions and influx of glutamate in in vitro and in vivo animal studies (Matis & Birbilis 2009). Experimental SCI studies in animal models to date have shown that EPO elicits a neuroprotective benefit that contributes to neurological recovery (Hong et al. 2011; Okutan et al. 2007). To date, there are four studies that have evaluated EPO for possible neuroprotection after SCI in humans.
Discussion
Although two early unblinded studies showed promising results for EPO in treating acute SCI (Alibai et al. 2014, Xiong et al. 2011), two subsequent, blinded studies failed to demonstrate benefit to EPO for neurologic outcomes post-SCI. It is important to note that all studies had very small sample sizes (n<70) and that in the positive trials, participants were neither blinded nor randomized. Both studies using randomized double-blind (Alibai et al. 2015) or single-blind (Costa et al. 2015) methodology did not detect a statistically significant difference between EPO and control, although sample sizes were small (n<30) and may have been underpowered to detect a difference. Large-scale blinded RCTs are warranted to determine the effectiveness of EPO in treating acute SCI. At present, there are no guidelines that recommend the use of EPO for neuroprotection in the acute phase of SCI.
Conclusion
There is level 1a evidence (from one double-blind RCT: Alibai et al. 2015; and one single-blind RCT: Costa et al. 2015) that acute administration of erythropoietin does not improve neurological outcomes post-SCI.
There is level 1b evidence (from one RCT: Alibai et al. 2014; and one prospective controlled trial: Xiong et al. 2011) that erythropoietin is effective in promoting neurological recovery in acute SCI individuals.
