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2004 World Technology Awards Winners & Finalists

Mark Tuszynski

Please describe the work that you are doing that you consider to be the most innovative and of the greatest likely long-term significance.

My colleagues and I have worked to develop innovative and effective therapies for some of the most common and lease treatable brain diseases, including Alzheimer’s disease and spinal cord injury. We have translated this work from basic animal studies to clinical trials in Alzheimer’s disease. Our approaches aim to harness the power of growth factors to prevent cell death in the brain, using methods of gene therapy.

It has been known for 20 years that growth factors prevent brain cell death. Thus, growth factors have remarkable potential to treat common, tragic and untreatable conditions including Alzheimer’s disease, Parkinson’s disease, ALS (Lou Gherig’s disease), and spinal cord injury. Unique among treatments, growth factors could prevent disease progression by rescuing cells from death. However, we have lacked safe and effective means of delivering growth factors to the brain. If administered peripherally, growth factors do not reach the brain in effective concentrations; if pumped into the brain, growth factors spread too widely and cause intolerable side effects.

Recognizing the need to develop effective and practical delivery methods for treating the brain with growth factors, we turned our attention to gene therapy. Made possible by the molecular biological revolution, gene therapy offers the possibility of delivering growth factors into precisely targeted brain regions containing degenerating cells, without growth factor spread beyond the intended area. This “precision-guided” nature of gene delivery in the nervous system makes it particularly attractive for obtaining proof-of-concept for the value of gene therapy to treat human disease, and offers a solution for delivering growth factors in human neurological disease.

Over 10 years ago we showed that growth factor gene delivery prevented cell death in rat models of Alzheimer’s disease. We subsequently demonstrated the effectiveness and safety of growth factor gene delivery in non-human primate brains. In 1999, we received approval from Food and Drug Administration to perform the first human clinical trial of growth factor gene therapy, treating the first patient with Alzheimer’s disease in April 2001. We have now treated 8 Alzheimer’s patients. The results of this clinical trial show a 50% slowing in disease progression over two-years. By comparison, drugs currently used to treat Alzheimer’s disease slow progression by only 5% for 3 - 6 months. NGF-treated patients also show significant increases in brain metabolic activity by Positron Emission Tomography (PET) scanning. Finally, examination of the brain of a patient who received growth factor gene therapy demonstrated an unequivocal growth factor response, the first such demonstration in the human brain. These findings support the concept that growth factors could be effective for treating and preventing progression of human neurological disorders.

Recently, Parkinson’s disease patients were treated with another growth factor; results similar to our Alzheimer’s study were reported, with one important difference: the Parkinson’s study pumped growth factors into the brain, rather than using gene therapy. The potential advantage of gene delivery of growth factors is clear: a single treatment would modify the brain to allow continuous delivery of the therapeutic growth factor without the risk of implanted hardware, and without the need to refill pumps or take drugs daily.

Our research has also shown the potential of growth factors to treat spinal cord injury. Injured connections of the spinal cord can be induced to grow into and beyond sites of spinal cord injury in rats. This research is now moving through non-human primates and, if effective, will also lead to human trials.

Neurological disease has been a realm broadly lacking effective therapies. Advances in molecular biology, cell biology and neuroimaging are converging to radically alter the therapeutic landscape for disorders of the brain.

Brief Biography

Mark Tuszynski, M.D., Ph.D., received undergraduate and M.D. degrees from the University of Minnesota in Minneapolis. He received clinical training in neurology at Cornell University Medical Center in New York City from 1984-1987, and became board-certified in neurology in 1989. He attended graduate school at the University of California-San Diego from 1988-1991, earning a Ph.D. in neuroscience. Dr. Tuszynski joined the faculty of the department of neurosciences at the University of California-San Diego in 1991. He is currently a Professor of Neurosciences at UCSD, Vice-Chair of the Department, and Director of the UCSD Center for Neural Repair.

Dr. Tuszynski’s research focuses on the role of growth factors in influencing plasticity and regeneration in the adult central nervous system. He actively researches the topics of aging, Alzheimer’s disease, spinal cord injury, and cellular mechanisms of normal memory.

In 2001 he began the first human clinical trial of gene therapy to treat an adult human neurodegenerative disease, testing the effects of nerve growth factor gene delivery in patients with early Alzheimer’s disease. He has won 8 national awards for neurodegeneration research, and is the author of over 130 scientific and medical publications. His articles have appeared in the journals Science, Nature Medicine, Proceedings of the National Academy of Science, Neuron, Journal of Neuroscience, and others.

Dr. Tuszynski directs the UCSD Center for Neural Repair, a collaborative interaction of 25 scientists aiming to understand mechanisms that contribute to cell death and regeneration failure in the adult nervous system, and to develop novel therapies to promote cell survival and regeneration. He has consistently accepted the challenge of testing novel, innovative approaches in the quest for more effective treatments for neurological disease. His work has both advanced understanding of basic mechanisms underlying nervous system function, and has led to new clinical trials in human disease.

In 2001, Dr. Tuszynski founded Ceregene, Inc., a biotechnology company developing growth factor treatments for human neurological diseases including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (Lou Gherig’s disease), and Huntington’s disease. With the understanding that large-scale clinical trials of growth factors will benefit from the resources and expertise of the private sector, the company has begun clinical trials that advance the programs developed by Dr. Tuszynski and colleagues in academia.

AWARDS: Presidential Scholar 1975 Tau Beta Pi Honorary Society 1977 Wasie Foundation Scholar 1980 National Research Service Award 1987 Physician Scientist Award 1988 Silvio O. Conte Physician-Scientist Award, American Academy of Neurology 1995 Elected to American Neurological Association 1998 Fellow, American Society for Neural Transplantation& Repair 1998 Bernard Sanberg Memorial Award for Brain Repair, American Society for Neural Transplantation & Repair 2000 C.U. Ariens Kappers Medal, Netherlands Institute for Brain Research 2001 National Paralysis Foundation Spinal Cord Injury Research Award 2001 Barbara Haugh Alzheimer's Disease Research Award 2002

SPECIALTY BOARDS: Board certification in Neurology, 1989.

ACADEMIC SOCIETIES: Society for Neuroscience American Academy of Neurology American Neurological Association American Medical Association International Brain Research Organization American Society for Neural Transplantation American Society for Experimental NeuroTherapeutics

BOARDS: Dr. Tuszynski serves on 6 editorial boards and 7 corporate and private scientific advisory boards. He serves on the council of the American Society for Neural Transplantation & Repair, and the Repair and Rehabilitation Committee of the American Neurological Association. He is Chair of the Basic Research Subcommittee of the American Neurological Association and Vice-Chair of the clinical practice committee of the American Society for Neural Transplantation & Repair.

BIOGRAPHICAL: Birthdate: February 27, 1959, Halifax, Canada. Citizenship: U.S. High School: Poway High School (California) and Burnsville High School (Minnesota). 1st in class. Advanced placement two years.