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30 years of ALS Genetics:  distinguishing Signal from Noise
ALS and Neurodegeneration Starts at the Nuclear Pore: Insights and Therapy for ALS and Dementia

ALS and Neurodegeneration Starts at the Nuclear Pore: Insights and Therapy for ALS and Dementia

Dr. Rothstein is Professor of Neurology and Neuroscience and a faculty member of the Graduate Program in Cellular and Molecular Medicine at Johns Hopkins University. He is the Founder and Director of the Robert Packard Center for ALS Research at Johns Hopkins. He is also the Director of the Brain Science Institute. He is also the Founder and Co-Director of the Johns Hopkins MDA/ALS Clinic. His team oversees one of the largest ALS clinics in the USA. Dr. Rothstein’s career has been highly focused on the identification of biological pathways that underlie and contribute to neuro-degeneration in ALS and the development of model systems to identify, test and validate therapies. These efforts began in the early 1990’ when his lab first discovered that excitotoxicity and mishandling of neurotransmitter glutamate might be a common pathophysiological process in sporadic ALS. This new concept and his experiments ultimately were the rationale for and use of riluzole ALS patients and its FDA approval. His research always employs a parallel analysis of model systems (e.g. mouse or human CNS cultures) and human tissues – as a validation of the relevance to real ALS. More recently, with the discovery of the C9orf72 gene mutation, his lab in collaboration with Ionis pharma, discovered the development of antisense oligonucleotides therapy for C9 ALS/FTD patients, and later, in collaboration with others, biomarkers that would be used to validate therapeutic target engagement in actual patients. In parallel with his drug discovery efforts, his lab has repeatedly made the discoveries on fundamental pathways that underlay familial and sporadic ALS including: excitotoxicity, astroglial dysfunction, oligodendroglial dysfunction and most recently, the role of nuclear pore complex and nucleocytoplasmic transport as one of the earliest pathophysiological event in familial ALS and likely sporadic ALS cases. Finally, aside from the many clinician scientists and basic scientists he has trained, he developed the Robert Packard Center for ALS research in 2000 as a model organization of mandatory academic collaboration and data sharing, the development of preclinical models and the free exchange of cutting edge ALS research. Recently he developed and founded the Answer ALS program - the world’s largest most comprehensive biological program to understand sporadic ALS and to be the starting point for “personalized medicine “ approach to ALS. The Answer ALS program is tasked with longitudinal clinical data and at home smartphone data collection and the generation of iPS neurons from each patient, and their comprehensive biological analytics- leading to a data set of 6 billion biological and clinical data points per patient. His program freely shares this enormous data collection to academic and companies worldwide.
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