The ability for regeneration and repair of the brain and spinal cord diminishes with age. This means that while spontaneous regeneration and repair can take place during development of a vertebrate, a big CNS injury during adulthood often leads to irreversible damage and functional deficits. In the past 20 years research has revealed that different inhibitory proteins in the CNS negatively affect nerve fiber outgrowth after injury. One of the most potent nerve fiber growth inhibitory proteins is Nogo-A which is mainly expressed in adult myelin, the insulating sheath surrounding axons.
After discovering and characterizing Nogo-A we developed means to supress the inhibitory function of Nogo-A with function blocking antibodies. In the animal model, anti-Nogo-A antibodies administered intrathecally or intracerebrally lead to regenerating and sprouting fibers as seen in histological sections and to functional recovery evaluated in a variety of behavioral tests: Rats with spinal cord injuries can perform locomotor tasks better and more precisely when treated with anti-Nogo-A antibodies compared to control animals, their bladder recovers faster and they are less prone to develop muscle spasms. These results suggest that new neuronal connections are formed which lead to functional recovery of the rats. Enhanced compensatory fiber growth, formation of new connections and a high level of functional recovery are also observed in brain lesioned rats and in experimental stroke following Nogo-A antibody treatment.