Monday, 16 April 2012

From Four Legs to Two - Translating Research Findings to Therapy of Spinal Cord Injury


Dogs and Spinal Cord Injury - Another Role for Man's Best Friend

Dr. Natasha Olby, VetMB, PhD, DACVIM (Neurology) Professor of Neurology and Neurosurgery at North Carolina State University College of Veterinary Medicine (NCSU CVM), studied at Cambridge University for her veterinary and research doctoral studies. She says it is at Cambridge where she first learned about the One Health application of animal models in biomedical research. After completing a postdoctoral study at Cambridge, she completed her residency in neurology/neurosurgery in North Carolina. As a board certified neurologist in the American College of Veterinary Internal Medicine, Dr. Olby joined the faculty at NCSU CVM where she has been conducting clinical work and research in spinal cord injury (SCI).

Dr. Natasha Olby discusses her work using dogs as models for spinal cord injury.

Dr. Olby began our session, “Benefits of Comparative Medicine: Regenerative Medicine?” with a holistic look at canine SCI research. Dr. Olby explored the ethical dilemmas and solutions of SCI research and explained that quantifying SCI recovery in dogs with naturally occurring spinal cord diseases is crucial in creating translatable data to improve human SCI treatments. She explained that adequate SCI models and outcome measures are imperative to improving SCI recovery. Dr. Olby explained that dogs are an appropriate model for human SCI because SCI is common and naturally occurring in dogs, it is comparable to human SCI, dogs are relatively large and uniform, clinical research avoids using laboratory animals and, as she showed during the presentation, the results are quantifiable.

Dr. Olby has advanced SCI treatments as she has created solutions for several hurdles in the field of SCI recovery. The gait scoring system she created for quantifying SCI recovery in dogs allows for advancements in recovery treatments as the field encompasses a variety of injuries, each with differing degrees of severity which each have specific goals and treatments. Since the severity of an injury will dictate the type of treatment an animal receives, Dr. Olby has been able to better identify successful treatments in SCI patients.

Dr. Olby continues to contribute to SCI treatment and recovery in her Canine Spinal Cord Injury Program. Through this clinical research program, Dr. Olby is able to test different treatments in specifically-defined groups of SCI patients and definitively report their outcomes. Her contributions to the advancement of SCI recovery in dogs is applicable to acute and chronic SCI patients and translates to human SCI suffers.

The Dalfampridine Story - The Making of a Medicine

Dr. Andrew Blight, PhD is the Chief Scientific Officer at Acorda Therapeutics and a member of the editorial board of the Journal of Neurotrauma. He began his session by outlining his unique path in One Health. Dr. Blight first became interested in SCI while studying the miniature potentials in frog spinal cord synapses. From there, he completed a postdoctoral study in Germany and subsequently became a Research Assistant Professor in the Department of Neurosurgery at New York University Medical Center. While there, Dr. Blight brought an interest in chronic SCI when he joined a research group studying acute SCI. From there, Dr. Blight became an Associate Professor of Anatomy at Purdue University School of Veterinary Medicine and then a Professor and Director of the Research Laboratory in the Division of Neurosurgery at the University of North Carolina, Chapel Hill. Dr. Blight continued to study the pathophysiology and treatment of SCI, which brought him to Acorda Therapeutics as head of research and development.

Dr. Andrew Blight describes the complex pathway from therapeutic concept to pharmaceutic approval and use.

Dr. Blight explained that while one would expect a linear transition from understanding of a dysfunction to conceptual solution, then animal studies, clinical studies, approval and use, this linearity is actually much more complex in drug development. He found this to be true while working on 4-aminopyridine; a drug therapy initially intended to treat SCI but ultimately approved for treatment of multiple sclerosis (MS). This drug is called dalfampridine in the United States and while its exact molecular mechanism is not understood, it has been shown to block unprotected potassium channels affected by multiple sclerosis demyelination and is effective at very low doses. 

Dr. Blight explained the long path this drug has taken in its journey to a Food & Drug Administration-approved drug. In the past, it has been used as an analeptic in anesthesia. It has also been used to treat botulism, myasthenia, Eaton-Lambert syndrome, Alzheimer’s disease, MS, and SCI. In Dr. Blight’s experience, there are many ups and downs in the development of a drug as clinical testing can have promising results, but these results can be hard to quantify. In Dr. Blight’s experience, the timed walk responder was found to be the most reliable measurement of treatment outcomes. Using an appropriate evaluation to measure the effect of dalfampridine also allowed them to elucidate the optimal dosage for dalfampridine in the treatment of MS. Thus, Dr. Blight provided an insider’s peek into the complex process of therapeutic drug development. 

Post authored by Josephine Drayton, NCSU MS Candidate in Animal Science & Nutrition

Up Next (17 April):
Going to the dogs … for a new model organism of non-Hodgkin lymphoma  
Steven Suter, VMD, MS, PhD, DACVIM, Assistant Professor, Oncology at NCSU CVM
                        Kristy Richards, MD, PhD, Assistant Professor Department of Genetics at UNC