Evaluating the effectiveness of anti-Nogo treatment in spinal cord injuries

Abstract

As humans, we cannot regenerate axons within the central nervous system (CNS), therefore, making any damage to it permanent. This leads to the loss of sensory and motor function below the site of injury and can be crippling to a person's health. Spontaneous recovery can occur from plastic changes, but it is minimal. The absence of regeneration is due to the inhibitory environment of the CNS as well as the inherent inability of CNS axons to form growth cones. Amongst many factors, one of the major inhibitory signals of the CNS environment is the myelin-associated Nogo pathway. Nogo-A, Nogo-B and Nogo-C (Nogo), stimulate the Nogo receptor, inhibiting neurite outgrowth by causing growth cones to collapse through activation of Rho Kinase (ROCK). Antibodies can be used to target this signalling pathway by binding to Nogo and thus promote the outgrowth of neuronal axons in the CNS. This use of anti-Nogo antibodies has been shown to upregulate CNS regeneration as well as drastically improve sensory and motor function in both rats and primates when coupled with adequate training. Here, we evaluate whether the experimental success of anti-Nogo at improving CNS regeneration can be carried over into the clinical setting to treat spinal cord injuries (SCI) and their symptoms successfully. Furthermore, we also discuss potential methods to improve the current treatment and any developmental obstacles.

Water Treadmill Training Ameliorates Neurite Outgrowth Inhibition Associated With NGR/RhoA/ROCK by Inhibiting Astrocyte Activation Following Spinal Cord Injury

“…The Nogo receptor family members NgR1 and NgR3 bind to CSPG, activating a signalling cascade via Rho family GTPases [9,29,30]. RhoA is the most important Rho family gene associated with nerve regeneration [7].…”

Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury

“…Treatments targeting growth cone function through the RhoA pathway have also been successful in promoting remyelination following CNS trauma. The IN-1 antibody, which neutralizes neurite growth inhibitors, has been utilized to infiltrate this signaling pathway (Mohammed et al, 2020 ). IN-1 MAb supports axonal regeneration following SCI (Schnell and Schwab, 1990 ; Brösamle et al, 2000 ).…”

Innovative IOP-Independent Neuroprotection and Neuroregeneration Strategies in the Pipeline for Glaucoma

“…A novel approach involves neuroprotection and neurorestoration via inhibition of the myelin-associated Nogo receptor pathway. Three CNS myelin proteins, Nogo-A, Nogo-B, and Nogo-C, stimulate the Nogo receptor, thereby inhibiting neurite outgrowth by causing growth cones to collapse through activation of ROCK [ 44 ]. The use of anti-Nogo antibodies has been shown to upregulate CNS regeneration, as well as improve sensory and motor function in both rats and primates with spinal cord injuries [ 44 ].…”

“…Three CNS myelin proteins, Nogo-A, Nogo-B, and Nogo-C, stimulate the Nogo receptor, thereby inhibiting neurite outgrowth by causing growth cones to collapse through activation of ROCK [ 44 ]. The use of anti-Nogo antibodies has been shown to upregulate CNS regeneration, as well as improve sensory and motor function in both rats and primates with spinal cord injuries [ 44 ]. In spinal-injured Sprague-Dawley rats, administration of the soluble function-blocking NgR ectodomain (NgR(310)ecto-Fc protein) causes axonal sprouting with subsequent correlation to improved spinal cord electrical conduction and improved locomotion [ 45 ].…”