Here’s as look at research that targets chronic spinal cord injury:
Recovery from chronic spinal cord contusion after Nogo receptor intervention, supported in part by the Reeve Foundation, from the Stephen Strittmatter lab at Yale.
Spinal cord injured animals recovered function with a treatment that didn’t start until two or three months after injury. In a mouse, that’s considered chronic. Indeed, in humans, 60 to 90 days is close to being chronic.
Strittmatter used two models: a hemisection injury (the cord is surgically cut but only half way); and a contusion injury, which more closely resembles most human injuries. His intervention used a decoy protein to tie up the receptor molecule (NgR1) for the axon-blocking inhibitor called nogo. A receptor, usually found on a cell surface, is the transfer point for a molecule outside the cell; block the receptor, block the transfer. So, no nogo, in this case, means go.
The work is based on Strittmatter’s work, Yale’s patents, and a new biotech,
Axerion Therapeutics.
Strittmatter used two approaches. In the hemisection animals, the nogo receptor was genetically eliminated. The animals showed improved locomotion. In the contusion group, animals were given the decoy protein intrathecally (directly administered to the spinal cord) for three months. Said Strittmatter, “Nogo decoy receptor therapy promotes recovery of function when treatment is initiated three months after injury.”
From the paper, in the Annals Neurology
Conditional deletion of NgR1 in the chronic state results in gradual improvement of motor function accompanied by increased density of raphespinal axons in the caudal spinal cord. In chronic rat spinal contusion, NgR1 decoy treatment from 4 to 6 months after injury results in 29% (10 of 35) of rats recovering weight-bearing status compared to 0% (0 of 29) of control rats (p < 0.05). Open field Basso, Beattie, and Bresnahan locomotor scores showed a significant improvement in the NgR-treated group relative to the control group (p < 0.005, repeated measures analysis of variance). An increase in raphespinal axon density caudal to the injury is detected in NgR1 decoy-treated animals by immunohistology and by positron emission tomography using a serotonin reuptake ligand.
Said Strittmatter: “This observation significantly extends the positive effect of NgR decoy receptor therapy seen in several previously published preclinical studies of acute and sub-acute spinal cord injury.”
Axerion, in a press release, wanted us to know this is not the same as the anti-Nogo treatment Novartis tested in Europe recently (results have not been published).
It needs 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.
Sylvia McBrinn, CEO of Axerion:
“As a target for intervention, chronic spinal cord injury has several distinct advantages over acute spinal cord injury including faster recruitment for clinical studies, stable baseline function when measuring recovery of motor skills and the potential to benefit a greater patient population. We are thrilled to observe the Nogo decoy receptor benefit in chronic spinal cord injury, and to note that the therapy also has applications in cases of stroke and glaucoma, among other indications.”
