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About Dr. Leon J. Thal



 

Leon J. Thal, M.D.

June 27, 1944 - February 2, 2007

  • Principal Investigator, Alzheimer's Disease Cooperative Study
  • Principal Investigator, Alzheimer's Disease Research Center
  • Chair, Department of Neurosciences, University of California, San Diego
  • Florence Riford Chair in Alzheimer's Disease, University of California, San Diego
  • Recipient, 2004 Potamkin Prize for Research in Pick's, Alzheimer's and Related Diseases
  • Recipient, 2007 Ronald Reagan Legacy Award

“Science knows only one commandment: contribute to science.” (Bertolt Brecht, The Life of Galileo)

Over the past three decades, Dr. Leon Thal translated intellectual vision and academic drive into a remarkable body of research productivity. He was one of the world's leading investigators engaged in the development of new therapeutics for Alzheimer's disease (AD) and was one of only a handful of scientists whose efforts significantly contributed to our understanding of the cause, prevention and treatment of AD and related disorders. His authority in the field was a magnet for training a new generation of scientists in the area of AD and dementia.

Dr. Thal's entire career was devoted to the study of aging and dementia. In the 1970's, he began aggressively pursuing the cholinergic hypothesis of AD. After investigations in the laboratory using rat and other models, he translated these studies to humans and subsequently performed clinical trials using choline, lecithin and other precursors of acetylcholine. In 1981, he published his finding that choline chloride failed to improve cognition in AD (Thal LJ, et al, Neurobiology of Aging 1981).

This lack of initial success challenged him to explore alternative and novel ways to treat the cholinergic deficit of AD using other compounds and routes of administration. The importance of this work was made evident by its publication in the highly regarded New England Journal of Medicine, (Thal L and Fuld PA, 1983). The studies provided some of the first evidence that memory could be enhanced in AD patients with cholinesterase inhibition.

Through continued efforts, despite occasional discouraging results, Dr. Thal's research continued to make marked advancements in the field. After nearly two decades of intense research activity, his efforts were rewarded with the approval of the first drug (a cholinesterase inhibitor) for the treatment of AD. In collaboration with Dr. Ken Davis, in the late 1980's he organized a landmark clinical trial for evaluating tacrine as a potential treatment for AD. This double-blind, placebo controlled, multi-center study was described in a second paper published in the New England Journal of Medicine and paved the way for approval of the compound in the United States. This work established his leadership in the testing and development of drugs for AD. Since that time, work with numerous cholinesterase inhibitors, as well as many other compounds, continues at an ambitious pace.

The strength of Dr. Thal's research effort and creative vision were best seen in his singular leadership in establishing major large scale clinical drug trials. It has been remarked that no single individual over the last decade had made a larger impact on the experimental therapeutics of AD than Dr. Thal in his capacity as the Principal Investigator of the NIH-funded Alzheimer's Disease Cooperative Study (ADCS). He was the guiding force in studies leading to the validation of instruments for evaluating the course of AD as well as the development of milestones for use in evaluating drug tests aimed at delaying the course of the disease.

The ADCS has fostered studies which have resulted in the change of clinical practice for patients with AD. On the basis of a single study again published in the New England Journal of Medicine (Sano M et al, 1997), vitamin E entered clinical practice for the care of patients with AD. Another ADCS investigation (Mulnard RA, et al, JAMA 2000) provided a definitive study to show that estrogen replacement therapy was not useful for the treatment of mild to moderate AD in women, despite its previous clinical popularity. Once again, Dr. Thal's efforts resulted in changing clinical practice.

In addition to his extraordinary efforts in clinical research, Dr. Thal's work also involved the enhancement of neuronal function and regeneration. Significant work in this area included showing that grafting nerve growth factor cells improved memory in the rat (Dekker AJ, et al, Neuroscience 1994.), and that grafting ACh cells has a similar effect (Winkler J, et al, Nature 1995).

The substantive contributions of Dr. Thal to the understanding, prevention and treatment of AD and related disorders during a period of more than three decades have resulted in providing new pathways for basic scientists to explore and created a new paradigm for clinical practice and diagnosis. His contributions to AD research will resonate through countless generations to come.

Dr. Thal died unexpectedly in February 2007.

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