| Biography | |
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 Prof. Martin Marsala University of California, USA |
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| Title: Spinal subpial AAV9 and cell delivery for treatment of neurodegenerative disorders. | |
| Abstract:
Effective in vivo use of adeno-associated virus (AAV)-based vectors to achieve gene-specific silencing or upregulation in the central nervous system has been limited by the inability to provide more than limited deep parenchymal expression in adult animals using delivery routes with the most clinical relevance (intravenous or intrathecal). Similarly current clinical protocols used to deliver cells into spinal parenchyma (as used in human spinal trauma or ALS trials) employ a direct needle penetration. As such this approach is very limited in achieving a wide-spread repopulation of spinal neuraxis by injected cells. In recent studies we have developed and validated a subpial vector and cell delivery technique in adult rat, pig and non-human primates. Collectively we have demonstrated that the spinal pia membrane represents the primary barrier limiting effective AAV9 and cell penetration into the spinal parenchyma after intrathecal cell or AAV9 delivery. Using adult rats and pigs we showed (i) potent spinal parenchymal transgene expression in white and gray matter including neurons, glial and endothelial cells at 14-28 days after single bolus subpial AAV9 delivery; (ii) delivery to almost all apparent descending motor axons throughout the length of the spinal cord after cervical or thoracic subpial AAV9 injection; (iii) potent retrograde transgene expression in brain motor centers (motor cortex and brain stem); and (iv) widespread cell migration of subpially injected human cortical stem cells at 6 months after cell delivery. We have also demonstrated the relative safety of this approach by defining normal neurological function for up to 6 months after AAV9 or cell delivery. Thus, subpial delivery of AAV9 or stem cells enables gene-based or cell-replacement-based therapies with a wide range of potential experimental and clinical utilizations in adult animals and human patients suffering from debilitating spinal neurodegenerative disorders including ALS, spinal trauma or multiple sclerosis.
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| Biography:
Martin Marsala is a Professor at the Department of Anesthesiology, at the University of California, San Diego, USA. Previously, he was a Senior Researcher at the Institute of Neurobiology, Slovak Academy of Sciences,Kosice, Slovakia. He holds a MD degree from the Safarik’s University of Kosice Medical School.He has published more than 160 peer review papers in journals indexed in the Web of Science including: European Journal of Neuroscience, Neuroscience, Experimental Neurology, British Journal of Pharmacology, Nature Medicine, Cell Metabolism, Nature, Cell Transplantation, Stem Cell Research and Therapy, Molecular Therapy Methods Clinical Development, ActaBiomaterialia, Neurosurgery, Neuron, PLoS One, Journal of Proteomics, Pain, Nature Neuroscience, Cellullar and Molecular Neurobiology, Expert Review in Proteomics, Spine Journal, Spinal Cord, Journal of Comparative Neurology, Proceedings of National Academy of Sciences, Journal ofHuntingtons Disease, Cell, Journal of Neurotrauma, ActaHistochemica and Journal of Neuroscience.He is on the review board of several journals including Experimental Neurology, Journal of Neuroscience, Neuroscience, Scientific Reports and Anesthesiology. He has participated in the scientific committee of several conferences and associations in USA, Japan and Europe. Currently, he is interested in pathophysiology of spinal-injury-induced muscle spasticity, chronic pain and cell-replacement therapies for treatment of spinal trauma and amyotrophic lateral sclerosis.
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