Accelerating Breakthrough Discoveries into Medicines

Stanley N. Cohen, MD

Dr. Cohen, known for being the co-inventor of recombinant DNA, is developing a therapy to treat Huntington’s disease (HD).

Stanley N. Cohen, MD is the Kwoh-Ting Li professor in the School of Medicine, professor of genetics, and professor of medicine at Stanford University.

In November 1973, a paper published in the Proceedings of the National Academy of Science by Cohen and his UCSF colleague Herbert W. Boyer described a methodology for propagating DNA, the hereditary material of all living cells, in foreign hosts. The invention of recombinant DNA or “genetic engineering” by Cohen and Boyer showed how any DNA could be inserted into, and reproduced by, the genetic machinery of bacterial cells.

The Cohen laboratory is now developing a therapy to address Huntington’s and other genetic neurodegenerative diseases that result from expansion of nucleotide repeat regions in specific human genes, generating mutant mRNAs and proteins that aggregate and destroy neuronal cells.

Studies published by the scholar and his colleagues in Cell and PLoS Genetics show that transcription elongation complex SUPT4H/SUPT5H is required for RNA polymerase II to proceed through DNA regions containing expanded NRs. Genetic interference with SUPT4H/SUPT5H complex formation selectively impedes synthesis of gene products encoded by expanded NRs, restoring neuron viability, and in mouse models, mitigating effects of the disease. Our findings have identified and validated a novel strategy and target for treating HD and other mechanistically similar diseases caused by NR expansions. This translational project aims to develop such therapy.

Huntington’s Disease and other nucleotide repeat diseases are monogenic disorders caused by synthesis of abnormal products by specific genes, and SUPT4H/SUPT5H knockdown decreases these mutant gene products, monitoring of blood cells from diseased patients enables non-invasive evaluation of drug efficacy. Experiments to identify additional components of the SUPT4H/SUPT5H pathway offer the prospect of combination therapies that decrease transcription through expanded repeats.

Dr. Cohen received his doctoral degree from the University of Pennsylvania School of Medicine in 1960. He joined the Stanford faculty in 1968 and has served as Chairman of the Department of Genetics there. He is the author of more than 360 scientific publications and the recipient of numerous honors and awards, including the National Medal of Science, the National Medal of Technology, the Lasker Award for Basic Medical Research, the Wolf Prize in Medicine, and the Shaw Prize in Life Science and Medicine. He and colleague Herbert W. Boyer are named as inventors on the basic patents underlying the field of genetic engineering.

Dates to Know

April 5, 2017
Letter of Intent Deadline

May 31, 2017
Full Application Deadline (For those invited)

December 2017
Awardees Notified

Harrington Project

The Harrington Discovery Institute is the nonprofit arm of the Harrington Project for Discovery & Development, an international initiative supporting breakthrough research by physician-scientists. The Project is a new and powerful approach to address some of the challenges hindering advancement of medicine today.

The Harrington Grant is an important part of the overall pharmaceutical research initiative created by The Harrington Project.

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