Spinal cord injury (SCI) is one of the most significant forms of neurotrauma with major economic and social impact.
Every year, nearly 12,000 individuals in the United States and Canada, mostly young adults, sustain a SCI. According to the Centers for Diseases Control and Prevention (CDC), SCI costs an estimated $9.7 billion each year in the United States alone. Although there are some early pharmacological and surgical interventions that may diminish the severity of SCI, the overall impact of these treatments remains minimal. “There is an urgent need for effective therapies to help restore neurological function in patients with acute SCI,” said Michael Fehlings, MD, PhD, FRCSC, FACS, head of the Krembil Neuroscience Center at the University Health Network in Toronto and a professor of Neurosurgery at the University of Toronto. Dr. Fehlings is leading a trial conducted in Canada and the United States, sponsored by BioAxone Therapeutique (Montreal, Canada), and more recently, Boston Life Sciences, Inc. to examine a novel treatment for individuals with SCI.
The findings of this study, Results of the Cethrin Phase I/IIa Prospective Clinical Trial of a Rho Inhibitor for the Treatment of Acute Spinal Cord Injury, were presented by Dr. Fehlings during the 75th Annual Meeting of the American Association of Neurological Surgeons in Washington, D.C. Co-authors are Nicholas Theodore, MD, James Harrop, MD, Gilles Maurais, MD, Charles Kuntz, MD, Christopher Shaffrey, MD, Brian Kwon, MD, Jens Chapman, MD, Albert Yee, MD, Patrick Tremblay, PhD, and Lisa McKerracher, PhD.
Without medical intervention, axons in the adult central nervous system cannot regenerate following SCI. Research, however, has shown the potential for regrowth of damaged axons. Recovery of function depends upon the severity of the initial injury. It is important that treatment is undertaken as quickly as possible because there is less chance of regeneration the longer the duration of the injury.
Researchers in Canada and the United States, led by Dr. Fehlings, are investigating the use of a novel Rho inhibitor, Cethrin®, (a recombinant protein) formulated with a fibrin sealant in patients with acute SCI. This drug has been shown to inhibit cell death and promote neural regeneration in animal models of SCI. Rho is a signaling master switch whose activation triggers cell death and increases damage after SCI.
Thirty-seven patients with acute SCI were enrolled in the one-year study at nine sites across Canada and the United States. All patients were classified with American Spinal Injury Association (ASIA) A SCI. That means they suffered a complete thoracic or cervical injury (i.e. having no sensory or motor function below the level of the SCI). ASIA grades are designated from A through E, with ‘A' designating complete SCI, and ‘E' being normal. Grades ‘B' through ‘D' designate decreasing levels of neurological involvement.
After patients underwent surgical decompression/reconstruction, treatment was initiated. This occurred within five days of the SCI incident, with the average time being 53 hours. Escalating doses of Cethrin® (0.3, 1.0, 3.0, and 6 mg.) were administered extradurally to the injured spinal cord. All adverse events were recorded and neurological outcomes were assessed using ASIA standards at 0, 1.5, 3, 6 and 12 months. The following outcomes were noted:
- There were no serious adverse effects related to Cethrin®.
- At 6 weeks, 30.6 percent of patients improved by one or more ASIA grades.
- The 6-month patient data showed that 28 percent of patients improved by one or more ASIA grades. Five patients improved to ASIA C and two patients improved to ASIA D.
- One patient with a thoracic SCI died from acute respiratory distress syndrome (ARDS).
“This preliminary research shows great promise for restoring some neurological function for patients with new cases of acute SCI. The positive findings in this Phase I/II trial provide the impetus to proceed to a prospective randomized trial,” stated Dr. Fehlings.
Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,800 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.