[NFS-02] The emergence of a new era of gene therapy and regenerative medicine in Neurology

[NFS-02-2] Block of neuraxial degeneration by silencing an ALS-causing mutant gene with subpial AAV9 delivery

Martin Marsala¹, Don W. Cleveland², Brian K. Kaspar³, Mariana Bravo-hernandez¹, Takahiro Tadokoro¹ (1.University of California, San Diego, USA, 2.Ludwig Institute for Cancer Research and Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, USA;, 3.Avexis Inc., Chicago, USA)

In 2017, an antisense oligonucleotide, nusinersen, was approved as the first treatment for spinal muscular atrophy (SMA). Nusinersen avoids the blood-brain barrier by being injected directly into the cerebrospinal spinal fluid space, and it also eclipsed the existing paradigm of neurological therapeutics. In addition, positive results of a clinical trial of SMA gene therapy using a neurotropic adeno-associated virus (AAV) type 9 were also announced. In 2018, furthermore, transplantation treatment using iPS cells / ES cells against Parkinson's disease was about to begin as an actual clinical trial.
At this symposium, world-leading scientists will talk about gene therapy / regenerative medicine with new modalities designed to overcome intractable neurological diseases.

Education: M.D., Safarik Medical Faculty, Kosice, Slovakia
General Medicine, 1986

Positions and Employment
1986-1992 Assistant Researcher, Inst. Neurobiology, Slovak Acad. Sci.
1992-1993 Postgraduate Research Anesthesiologist, Anesthesiology Research Laboratory, UCSD
1993-2000 Assistant Research Scientist, Anesthesiology Research Laboratory, UCSD
2000-2006 Associate Adjunct Professor, Anesthesiology Research Laboratory, UCSD
2006-present Professor, Anesthesiology Research Laboratory, UCSD

Summary of research interest(s):
During the past 20 years I have been involved in the development and characterization of several spinal ischemia and trauma models. My laboratory has characterized the behavioral, electrophysiological and histopathological changes in the spinal cord and brain of animals after transient ischemia or trauma. As a part of these studies, we have i) developed a technique of spinal cord injections to permit region-specific cell or vector delivery, ii) characterized the optimal and safe cell dosing regimen after grafting of human spinal stem cells, and iii) characterized a long-term effective immunosuppression protocol in minipigs which permits effective xenograft survival. In addition, more recently we have successfully generated porcine iPS and fetal brain/spinal cord-derived neural precursor lines and have demonstrated long-term survival after in vivo grafting in naive immunodeficient rats or immunosuppressed minipigs. I have published over 170 peer-reviewed articles (with around 4500 citations).