Preclinical Evidence of Nogo-A Inhibition in Stroke Recovery: A Scoping Review

Stroke is one of the leading causes of disability worldwide. Although preclinical studies have shown promising results of pharmacotherapies to enhance stroke recovery, no drug has been approved for stroke recovery in patients. In this article, we review the preclinical data of one promising treatment, inhibition of NgR1 (Nogo receptor 1) signaling, for stroke recovery. Our scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews and surveyed the peer-reviewed literature on PubMed and citation searching. Studies were eligible if they evaluated the pharmacological inhibition of Nogo/NgR1 signaling in nonhuman models of stroke assessing sensorimotor or functional outcomes. There were no restrictions in years considered. An assessment of the risk of bias was performed using the Systematic Review center for Laboratory Animal Experimentation tool. Three hundred seventeen articles were screened based on the inclusion criteria. Thirty preclinical studies were included. Most studies (90%) were conducted in rodents, with only 3 studies (10%) completed in nonhuman primates. Anti-Nogo-A antibody was the most common pharmacological intervention, used in 21 (70%) studies. Most preclinical studies delivered the study drug directly into the central nervous system (intrathecal, intraventricular, or intraparenchymal), with far fewer studies (n=5) testing subcutaneous, intravenous, or intranasal administration. Among the 30 studies included, 27 (90%) report a beneficial effect. In conclusion, there is a large body of preclinical evidence to support Nogo/NgR1 inhibition in promoting stroke recovery. A clinical trial to assess the safety, feasibility, and efficacy among patients with stroke is warranted.