Columbia University in the City of New York

Feb 19, 20194:00 pm

Designer DNA Drug Therapy for Human Neurodegenerative Disease

Featuring Don W. Cleveland, PhD, Distinguished Professor and Chair, Department of Cellular and Molecular Medicine, University of California, San Diego (UCSD)

February 19th, 4:00 pm – 5:00 pm at the Neurological Institute of New York (1st floor)

This seminar will be held in the Neurological Institute of New York's Auditorium (1st floor). Columbia University's Intercampus Shuttle Service is the best way to travel between campuses.

The genes whose mutation causes neurodegenerative disease are widely expressed within neurons and non-neurons of the nervous system, producing damage not only within the most vulnerable neurons but also within their partner neurons and supporting glia. Sustained gene silencing within neurons and non- neurons throughout the nervous system has been achieved using a clinically feasible approach with “designer DNA drugs”. Single doses have been shown to produce sustained suppression of the target gene (mediated by catalytic degradation of the RNA intermediate copied from that gene). In rodents, this approach has slowed disease progression in genetic mimics of inherited ALS and has produced prolonged, partial disease reversal in models of Huntington’s disease. A similar designer DNA drug has successfully corrected an error in the assembly of an RNA intermediate, thereby restoring production of the gene product whose absence is the cause of spinal muscular atrophy (SMA), one of the most abundant inherited diseases of children. For the most frequent genetic cause of both ALS and the second most frequent dementia (frontal temporal dementia), single dose administration of a designer DNA drug has reduced the synthesis of the toxic product of the mutated gene and prevented age-dependent cognitive disease. Multiple clinical trials to suppress genes contributing to ALS, Huntington’s, and Alzheimer’s diseases are now underway. Extensions of these designer DNA drugs are in development to permanently inactivate disease- causing genes in the nervous system or to induce the generation of new neurons to replace those lost during disease or normal aging.

Dr. Don Cleveland has made field leading contributions in cancer genetics and neurosciences. He is currently Professor and Chair of the Department of Cellular and Molecular Medicine at the University of California at San Diego, as well as a member of the Ludwig Institute for Cancer Research. A graduate of New Mexico State University, he has been elected to the U.S. National Academy of Sciences and National Academy of Medicine. In December 2017 he received the $3M Breakthrough Prize in Life Sciences for his development of a new class of “designer DNA drugs” for silencing disease-causing genes responsible for the major diseases of the nervous system, including ALS, Huntington’s, Parkinson’s and Alzheimer’s diseases. He initially identified tau, the protein which accumulates aberrantly in Alzheimer’s disease and which is the protein whose misfolding underlies chronic traumatic brain injury (now receiving international attention from its impact in athletics, especially American football). He uncovered the mechanisms underlying the major genetic forms of Amyotrophic Lateral Sclerosis (ALS) and demonstrated that disease involves neurons and their non- neuronal neighbors. He has developed gene silencing therapy for neurodegenerative diseases using designer DNA “antisense oligonucleotide (ASO)” drugs. Clinical trials with these ASOs have been initiated for multiple neurodegenerative diseases, including for ALS and Huntington’s diseases.

Those who wish to meet the speaker during their visit should contact Christopher Griffey (Yamamoto lab). For general inquiries please contact

The Columbia Neuroscience Seminar series is a collaborative effort of Columbia's Zuckerman Institute, the Department of Neuroscience, the Doctoral Program in Neurobiology and Behavior and the Columbia Translational Neuroscience Initiative, and with support from the Kavli Institute for Brain Science.

Venue: the Neurological Institute of New York (1st floor)
710 W 168th St, New York, NY 10032

Connect with us