Can spinal cord injuries be reversed?

Neuroprotection: Drugs that rescue spinal tissue
“Neuroprotection salvages cells that would otherwise die,” says Dr. John Hurlbert, a spinal neurosurgeon who launched the minocycline trial with Dr. Steve Casha, a fellow University of Calgary neurosurgeon. “It’s easier to save neurons than to regenerate them.”

Minocycline does that by reducing neuroinflammation and blocking the release of toxic chemicals that would otherwise destroy healthy cells near the primary injury site. The drug must be given within 12 hours to keep those cells from dying and then administered twice daily for seven days.

For newly injured patients such as Franci, the hope is that neuroprotective drugs can stop the secondary wave of cell suicide that sweeps through spinal cord tissue and lead to a fuller recovery. The more tissue that is preserved, the more movement and sensation the patient is likely to regain in the weeks, months and years after the injury.

Franci is one of 50 patients participating in the minocycline study; half were treated with the drug and half were given a placebo. Although Franci won’t know whether she was treated until the study is completed next year, she and her husband remain optimistic. “We have an intuition that Franci is on minocycline,” says Karl. That belief could be based simply on hope, or on the progress in her hand and finger movements in the months following her injury.

Neuroprotection and regeneration: Repair the cord, grow new nerve endings
Cethrin, a new drug developed by Lisa McKerracher, formerly a neuroscientist at the Université de Montréal, has both neuroprotective and regenerative properties. Scientists have learned in the last decade that spinal cord cells can potentially grow new connections, but certain inhibitory molecules released after a spinal injury prevent regeneration.

Ten years ago, McKerracher developed a protein molecule, called Cethrin, that blocks Rho (which receives signals from those inhibitory molecules). Preclinical studies showed that Cethrin greatly improves recovery after a spinal injury because it prevents cells from dying and promotes regrowth of injured axons (nerve cell fibres that carry messages).

In 2005, Bioaxone Therapeutic (a biotech company started by McKerracher) launched a clinical trial of the new drug at hospitals in Toronto, Montreal and Vancouver, and in five cities in the United States. Thirty-seven patients with complete spinal cord injuries had the drug topically delivered onto their spinal cords within eight hours of the injury. (Patients – like Franci – who have complete injuries have no movement or sensation below the injury site and are much less likely to regain them than patients with incomplete injuries.)

The results are very encouraging. About 31 per cent of patients recovered some sensation and/or movement below the level of the injury, going from a complete to an incomplete injury. The drug is safe, and those patients will have a much better chance of regaining more mobility in the future. “The data look better than anyone could have expected from a safety trial,” says McKerracher.

The Cethrin trial was led by spinal surgeon Dr. Michael Fehlings, holder of the Krembil Chair in Neural Repair and Regeneration at the University Health Network’s Toronto Western Hospital. “The degree of improvement in patients treated with Cethrin exceeds expectations, and Cethrin shows great promise,” says Fehlings, noting that seven patients improved substantially, with at least two regaining some movement in their previously paralyzed legs.

In January of this year, Alseres Pharmaceuticals acquired the rights to develop and commercialize the drug, and the company plans to launch a large clinical trial early in 2008 to definitively assess the benefits of Cethrin for spinal cord patients.

Page 3 of 6