Jose Eduardo Espindola Lima1, Sophie Rengarajan1, Anna-Sophia Wahl2, Paul George3, Kevin Sheth4, Maarten Lansberg5
1Stanford Neurology, 2Institute for Stroke and Dementia Research, LMU Klinikum and Institute of Anatomy, Ludwig-Maximilians-Universität München, 3Stanford Hospital, 4Yale UniversityDivision of Neuro and Critical Care, 5Stanford Stroke Center
Objective:
Summarize preclinical data on Anti-Nogo-A antibodies, NgR1 decoy receptor and antagonists of Nogo/NgR1 signaling in stroke recovery and to examine whether results favor additional clinical studies in stroke.
Background:
Stroke is a leading cause of disability worldwide. While preclinical studies have shown promising results of pharmacotherapies to enhance stroke recovery, no drug has been approved for this purpose. Nogo inhibition promotes stroke recovery in animal models, and recent trials of Nogo inhibition in spinal cord injury suggest safety, tolerability, and efficacy in humans.
Design/Methods:
Our study followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews (PRISMA-ScR) recommendations. A Pubmed search and citation searching for articles on Nogo inhibition in animal models of stroke was performed with the assistance of a librarian.
Results:
298 articles were identified. Of those, 261 were excluded based on title and abstract being non-responsive to the topic. After reviewing the full text of 37 articles, 5 additional articles were excluded, leaving 32 studies for inclusion. Experimental models of stroke, pharmacological interventions, and functional outcome assessments varied between studies. 90.6% of the studies were conducted in rodents and 9.4% in non-human primates. The most common pharmacological intervention was anti-Nogo-A antibodies (72%). Three studies combined pharmacological interventions with motor training. The forelimb grasping test was the most commonly used functional outcome test (53%). A positive treatment effect was observed in 87% of the studies.
Conclusions:
There is substantial preclinical literature to support the benefit of Nogo inhibiton. Coupled with the existing safety data of Nogo inhibition in patients with spinal cord disease, this supports a trial of Nogo inhibition in patients recovering from ischemic stroke. Further research on Nogo inhibition would benefit from standardization of methods (e.g., dosing, time of intervention, assessment of functional outcomes) and the combined treatment with rehabilitation programs compared to pharmacological treatment alone.