New discoveries in spinal cord regeneration research were unveiled by a superb panel of well known spinal cord investigators during a press conference at the 40th Society for Neuroscience conference in Chicago, Il. During the last ten years, animal research has suggested new ways to speed the recovery of damaged spinal cord in patients. New methodologies and techniques were discussed at today’s morning press conference which included the development of a novel diet, the use of nerve growth factors and the enhancement of stem cell therapy techniques which enable the speedy and smooth recovery of damaged spinal cord or sensory nerves that attach to the spinal cord.
Overall, these findings will help to mold and re-design existing therapies for spinal cord injury, a devastating condition that affects more than one million Americans each year.
The distinguished panel of lead investigators who conducted these studies and presented their findings during the morning press conference include Dr. Wolfram Tetzlaff from International Collaboration on Repair Discoveries, British Colombia; Dr. Nakamura, from Keio University School of Medicine, Tokyo, Japan; and Dr. Erik Frank from Tufts University School of Medicine, Boston, MA.
In a nutshell, the research released today is summarized here:
1. Patients that have sustained spinal cord injury are usually given very high calorie diet alternative which consist of ingesting large amounts of carbohydrates but low amounts of fat. These diets have never been validated or approved by any medical or professional board in the United States. On the other hand, fasting has been previously shown to speed the spinal cord injury recovery although this alternative is much more controversial and less popular in the medical field.
A new, re-designed ketogenic diet that is low in carbohydrates but high in fats was found to speed the recovery of rats that have undergone spinal cord contusion. The effects of the ketogenic diet in a rat model of spinal cord injury was impressive. After 15 weeks of being fed the ketogenic diet, Dr Tetzkaff found that a little over more than 50% of rats used their injured paws 15 times more frequently than rats fed a standard control diet. Moreover, ketogenic diet fed rats used their forelimbs five times more than the control group. It is important to note that all groups of rats were fed the same amount of calories regardless of the diet employed in the study. This is a significant finding with practical applications to human beings that suggests that the dietary content and quality of therapy has a significant impact on the recovery of patients. Other practical applications of a ketogenic diet proposed by the author of this study include employing this diet for the treatment of patients suffering neurodegenerative diseases such as Parkinson’s disease and amyotrophic lateral sclerosis.
2. The second interesting study with relevance to spinal cord research was conducted by Dr. Nakamura form Keio University School of Medicine in Japan. It is widely known that induced pluripotent stem cells derived from adult somatic cells have the potential for curing a variety of central and peripheral nervous system diseases. Once IPS cell lines are established, a cocktail of growth factors can then be employed to differentiate IPS to different types of cells, including connective tissue, bone and neuronal cells. The main goal is to use these differentiated cells for regenerating a damaged tissue in a patient that suffered injury. Interestingly, IPS cells are currently been grown in different scaffolds or molds which may be implanted in patients suffering from osteo-arthritis in order to reform the lost bone structure and composition.
However, one serious drawback of using IPS or embryonic stem cells for spinal cord injury is the potential of transplanted IPS cells to regress into a cancer-like state or the formation of malignant tumors such as teratomas. To circumvent this problem, Dr. Nakamura showed novel techniques that can be used to screen for multiple clonal stem cell lines for tumorigenic (cancer causing) potential. More importantly, the use of these tumor pre-screening techniques may result in life saving treatments without the presence of such side-effects. To increase the repertoire of IPS cell lines that can be used in the future, the authors of the study painstakingly developed up to 36 different human IPS lines that differed in origin (adult somatic cell) and in phenotypic characteristics.
In brief, their results showed that it is better to use more matured and developed IPS stem cells than immature IPS cells, the latter being problematic as it has a higher tendency to form teratomas. Moreover, the use of certain IPS cell lines had a tendency to develop into neurons, glia cells (support cells for neurons) and into oligodendrocytes, cells that produce myelin which is a lipid-protein component of spinal cord necessary for increasing the speed of electrical conductivity of the spinal cord. These techniques will enable transplantation therapy to be much safer and efficient by examining different types of stem cell lines. Future work is needed to determine the efficacy and safety of all 36 human IPS cell lines in humans.
3. Finally, the third spinal cord research breakthrough was explained by Dr. Eric Frank from Tufts University School of Medicine, Boston, MA. A secondary side effect of head and neck injuries involves the possible resection, and permanent damage of sensory and pain neurons of the brachio-plexus area (near the shoulder blade) that connect to the spinal cord. Sensory nerves gets stretched or destroyed during a traumatic head injury or car accident and researchers and medical doctors are trying to find therapies that can mediate the healing of these nerves.
Dr. Frank discussed recent progress in regeneration research carried out by different investigators whose goal is to regenerate and guide de novo sensory axons that lead to the human spinal cord. Dr. Frank’s group found that administering Artemin , a pharmaceutically reformulated form a type of nerve growth factor leads to the regeneration of sensory nerves. In addition, adding a ligand specific for the Nogo receptor, which blocks inhibitory signals for neuronal development, in conjunction with systemic administration of neurotrophic factors (nerve growth factor and glial derived nerve growth factor) leads to a more robust and enhanced regeneration of axons and better reconnectivity to the spinal cord. Moreover, Dr. G.M Smith from the University of Kentucky found that administering nerve growth factor and a chemorepulsive agent called semaphorin-A improves the regeneration and reconnection of axons to the spinal cord by reducing the number of regenerating neurons, which suggests a more effective synaptic connectivity.
Dr. Frank made the analogy that nerve growth factor treatment is like opening more highways through which more traffic can flow but without any guidance or direction which eventually leads to a bottle neck. Thus, adding semaphoring-A, a chemorepulsant of axonal guidance, is like having a traffic cop regulating not only the volume of traffic but increase the direction and flow of traffic to their right destinations.
Finally, press conference moderator Oswald Steward, Ph.D. of the University of California, Irvine, an expert spinal cord injury mentioned “We are learning a great deal about how to encourage the recovery process and harness the plasticity of nervous system to offer hope to spinal cord injury patients”. Although this final statement seems to bring more light and hope to the field of spinal cord regeneration, there is still more work to do in the future with regards to translating some of the research found at the basic level to the clinical level which will greatly depend on pumping millions of research dollars that will enable the push for the approval of neurotrophic factors and IPS cell lines for spinal cord injury patients. On the other hand, gaining approval of a ketogenic diet in spinal cord injury clinicals may not have such a bumpy road with the FDA as approving the other techniques.
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As a follow up to this article, you may want to read this article that was published today about treatments using stem cells already being done in Germany.
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