Neurotherapeutics in the Era of Translational Medicine

Table of Contents

1. Development of a molecular therapy for the SOD1 familial variant of ALS
2. Unraveling molecular biology of C9ORF72 repeat expansions in amyotrophic lateral sclerosis-frontotemporal dementia: Implications for therapy
3. Translating molecular therapies for spinal muscular atrophy
4. From uncovering the mechanism of transthyretin aggregation to the drug tafamidis for ameliorating neurodegeneration and cardiomyopathy
5. A novel treatment for Parkinson's disease and ALS: Combined cell
and gene therapies
6. Parkinson's disease: Genetic-driven therapeutic approaches
7. Neural stem cell-mediated brain tumor therapy
8. Advances in migraine therapeutics: The role of calcitonin
gene-related peptide
9. The impact of translational research on the development of therapeutic
agents for multiple sclerosis
10. Advances in treating myasthenia gravis�
11. The endocannabinoid system as a target for the treatment
of neurological disorders
12. Identification of biomarkers for diagnosing and monitoring therapy in the treatment of neurologic disorders
13. 3D Alzheimer's disease in a dish: Implications for drug discovery
14. Improving clinical trial efficiency with machine learning models
of disease progression
15. Positron emission tomography imaging agents for evaluating the pathologic features of Alzheimer's disease and drug development�
16. Repurposing FDA-approved pharmaceuticals: The development
of Nuedexta
17. Bioethics in the era of translational medicine
18. Government efforts to promote the development of neurotherapeutics for the treatment of neurological diseases
19. Innovative funding models for neurotherapeutics

Authors

Richard A. Smith Director, Center for Neurologic Study, La Jolla, CA, USA. Dr. Smith is the Director at the Center for Neurologic Study in La Jolla. During his neurology residency at Stanford University, Dr. Smith began his first studies of Lou Gehrig's Disease which has remained his principal career interest. His initial studies focused on the symptomatic treatment of ALS but at Scripp's Research Institute, he began to research the cause of ALS and subsequently directed his major effort to developing a therapy for ALS and kindred disorders. His earliest publications in the New England Journal, British Medical Journal, etc. were among the first to demonstrate the utility of symptomatic management in the care of ALS patients. Dr. Smith was one of the first investigators to recognize the potential of interferon as a treatment modality for neurologic disorders, and his work on the pharmacology of interferon contributed to the adoption of interferon as a treatment for multiple sclerosis. Along with colleagues Barry Festoff and Schlomo Melmed, Dr. Smith conducted the first trial of a growth factor (IGF-1) as a potential treatment for neurological disorders. More recent achievements include the development of DMQ which was approved by FDA in 2011 for the treatment of emotional lability associated with ALS and kindred diseases. Last July, in a nationwide controlled study, he and his colleagues demonstrated enhancement of speech and swallowing in ALS. This medical milestone is unique in that no pharmacologic intervention had ever improved function in this disorder. Perhaps his most notable achievement is his realization that it would be possible to downregulate the expression of gene products in the central nervous system using antisense therapeutics. This work was undertaken with Don Cleveland (UCSD) and Ionis Pharmaceutical Corp. Last year, the FDA approved Spinraza, an antisense product for the treatment of spinal muscular atrophy (SMA1), and in the last few months, Roche Pharmaceuticals announced that their Phase 1/2 treatment trial of Huntington's disease was a success. The endpoint for this study was the reduction of Huntington protein in the spinal fluid. Based on this result and preclinical work in animals, there is reason to believe that this treatment strategy will result in the first meaningful therapy for Huntington's. Brian K. Kaspar Scientific Founder, Milo Biotechnology, San Diego, CA, United States. Dr. Kaspar is the scientific founder of Milo Biotechnology, a gene therapy company focused on muscle regeneration. He was formerly Principal Investigator in the Center for Gene Therapy, Associate Professor in the Department of Pediatrics and Department of Neuroscience at the College of Medicine in the The Research Institute at Nationwide Children's Hospital in Columbus, Ohio and has founded several biotechnology companies such as AveXis where he served as CSO and Celenex. Clive N. Svendsen Director, Board of Governors Regenerative Medicine Institute, Cedars-Sinai, Advanced Health Sciences Pavilion, Los Angeles, CA, USA. Dr. Svendsen did his pre doctoral training at Harvard University and received his PhD from the University of Cambridge in England where he then established a stem cell research group before moving to the University of Wisconsin in 2000 to became Professor of Neurology and Anatomy, Director of an NIH funded Stem Cell Training Program and Co-Director of the University of Wisconsin Stem Cell and Regenerative Medicine Center. In 2010 he moved to Los Angeles to establish and direct the Cedars-Sinai Regenerative Medicine Institute which currently has 15 faculty members and approximately 100 staff. One focus of his current research is to derive cells from patients with specific disorders which can then be "reprogrammed" to a primitive state and used as powerful models of human disease. Dr. Svendsen led the first groups to successfully model both Spinal Muscular Atrophy and more recently Huntington's Disease using this technology. The other side of his research involves cutting edge clinical trials. He was involved with one of the first growth factor treatments for Parkinson's Disease and is currently working closely with neurosurgeons, neurologists and other scientists to develop novel ways of using stem cells modified to release powerful growth factors to treat patients with neurological diseases such as ALS, Huntington's, Alzheimer's and Parkinson's.