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Clinical Trial Enrolling Chronic SCI

Biotech start-up ReNetX has begun enrolling people with chronic cervical spinal cord injuries in a clinical trial to test a molecular cocktail called Nogo Trap.

This is a two-part trial that will eventually include 66 patients. Each participant will be given a dose of Nogo Trap, called AXER-204 by the company. The drug is given via lumbar puncture, a procedure not considered risky but requires admission to the hospital. Part I will evaluate the safety, tolerability, and pharmacokinetics (how the drug acts in the body) of single ascending doses of AXER-204. Part II, set for next year, will look at the same things, but with repeated doses, and also comparing the drug to placebo.

Are you eligible? Your injury has to be at least a year old, and must involve the cervical spine. Trial protocols do not indicate function by level of injury, but by motor scores: “Bilateral ISNCSCI score between 4 and 36 points inclusive, and bilateral GRASSP Prehension Ability score between 4 and 12 points inclusive.” Since most people have no idea what those numbers mean or what their own motor scores are, it comes down to this: you must have some arm and finger impairment.

How does Nogo Trap work: It can be thought of as a decoy: it attracts and thus cancels out inhibitory molecules that show up when myelin is damaged after spinal cord trauma. These blocking agents have aptly been called Nogo: decoy these bad myelin inhibitors and stuck nerves are able to grow past them, and perhaps to restore connections and function. The ReNetX trial targets three anti-Nogo molecule variants, Nogo-A, MAG, and OMgp.

ReNetX is based to a large degree on the work of Stephen Strittmatter, M.D., Ph.D., who directs the Cellular Neuroscience, Neurodegeneration and Repair unit at Yale. Strittmatter got his science credentials in 1986, about the time Nogo was first characterized by Swiss scientist Martin Schwab, Ph.D. By the late-1990s Schwab had figured out how to clone Nogo, thus opening up a vast field of study to many more investigators, including Strittmatter.

For many years we’ve seen data indicating that anti-Nogo therapy is a genuine boost to recovery after experimental paralysis in animals – but only if given soon after injury or stroke, usually within a week.

(Indeed, Schwab has started a company too, NovaGo Therapeutics, based in Switzerland, also developing an anti-Nogo therapy for cerebral stroke and spinal cord injury to stimulate nerve repair and regeneration. NovaGo is running a placebo controlled, randomized, double blind, multicenter, multinational study, enrolling 132 patients at 13 European hospitals, delivering anti-Nogo-A to acute SCI patients, within 4 to 28 days of injury; see trial here, or here.)

Strittmatter, however, discovered an anti-Nogo pathway that could be decoyed in a chronic SCI contusion model. In 2011 his group at Yale published a paper “Recovery from Chronic Spinal Cord Contusion after Nogo Receptor Intervention.”

This paper, which becomes a bridge to his formation of ReNetX and the Nogo Trap trial, reported that a decoy for a Nogo-related molecule called NgR1 improved motor function in rats that had been paralyzed for three months (in a small animal, that is considered chronic). One third of treated animals recovered weight-bearing hind limb function. Open field locomotor scores were significantly improved in the NgR-treated group relative to the control group.

What gives? Apparently there are nerve axons surviving in a long-term spinal cord injury that respond to a little chemical nudge. Says the paper, “We reasoned that because many axonal tracts and intrinsic spinal circuits remain intact in regions proximal and circumferentially to SCI sites and are continually exposed to myelin and myelin debris, blockade of myelin inhibitors long after spinal injury might stimulate axonal growth and recovery.”

OK, great for rodents but is the model relevant to humans? ReNetX hopes so. They say there is non-human primate data being published soon that will show a Nogo Trap effect. The company suggests the treatment increases plasticity of synapses (nerve to nerve connections), increases short-range axon growth and even promotes some degree of long-range axon growth – and in a chronic spinal cord injury model.

The Nogo Trap trial is taking place at these major U.S. centers:
Keck Medicine of USC, Los Angeles
Shepherd Center, Atlanta
Shirley Ryan AbilityLab, Chicago
Thomas Jefferson University, Philadelphia
Ohio State University Wexner Medical Center, Columbus

ReNetX suggests that if you want to consider participating, contact one of the centers. You can get the numbers here at the clinicaltrials.gov listing.

Kudos to Wings for Life for supporting ReNetX and its trial, and also for partly funding the NovaGo trial.