Functional recovery in a chronic spinal cord injury model

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The recovery observed with the Nogo Decoy Receptor treatment was measured by monitoring several parameters in animal trials. Those included motor score, weight-bearing status and computerized limb kinematics, all of which reflect the walking ability. A three months treatment allowed 29% of chronic injured animals to regain the ability to bear weight and walk. These functional improvements were linked to an increase in axon density caudal to the injury, meaning that the treatment was promoting effective neuronal regeneration (please see the illustration).

A “chronic disease” is defined as a disease that persists for a long time (3 months or more). Due to the higher difficulty of achieving effective functional recovery in chronic spinal cord injuries, most research projects focus on acute or sub-acute preclinical models. On the other hand, chronic spinal cord injury has several advantages including the potential to benefit a greater patient population, quicker recruitment for clinical studies and a stable baseline function when measuring recovery of motor skills.

It need to be emphasized that the new compound tested, NgR1 decoy receptor protein is a novel development not to be mixed up with earlier, limited attempts blocking the growth inhibitory function of the Nogo-1 receptor (NgR1) only partially (NEP1-40). NgR1 decoy receptor protein is a soluble truncated NgR1 fusion protein (NgR (310)-ecto-Fc)– which prevents binding of several growth inhibitory proteins to NgR1 receptor. This consequently neutralizes all 3 myelin inhibitors such as Nogo-A, MAG and OmGP. Therefore, this blocking strategy is more potent than the previous compound NEP1-40, which only stopped the binding of one growth inhibitory molecule, Nogo-A.

These promising results, combined with the fact that the therapy has also applications in other indications like stroke or glaucoma, make of the Nogo decoy receptor protein a very interesting clinical target. The US Company Axerion is currently developing the Nogo decoy receptor  for the treatment chronic spinal cord injury that might be later used on human subjects within a controlled clinical trial.

Recovery from chronic spinal cord contusion after Nogo receptor intervention.
Wang X, Duffy P, McGee AW, Hasan O, Gould G, Tu N, Harel NY, Huang Y,
Carson RE, Weinzimmer D, Ropchan J, Benowitz LI, Cafferty WB, Strittmatter
SM. Ann Neurol. 2011 Nov;70(5):805-21.