Basic science research on cellular functions yields a surprising discovery

November 1, 2004

WORCESTER, Mass.-   The observation came during their work studying cellular processes within the heart.  In that effort, University of Massachusetts Medical School (UMMS) scientists James G. Dobson, Jr., PhD, professor of physiology and medicine, and Michael F. Ethier, PhD, assistant professor of medicine, were probing the effects of aging on heart function. Little did they realize that their work with adenosine would lead to the creation of a cream that improves skin tone and diminishes wrinkles.

"The results took us completely by surprise, but that's what happens in basic science work," Dr. Dobson said. "The science often leads us down unexpected paths."

Adenosine is a naturally occurring nucleoside found in many cells of the body.  Among its other attributes, adenosine is known to play a role in helping the heart muscle and vascular walls contract and relax. Drs. Dobson and Ethier were studying adenosine in a series of experiments probing the effect of aging on the cellular functions within the heart. "In that work, we began using dermal fibroblasts, which are skin cells, because they have well-defined aging characteristics," Dr. Ethier said. "Skin cells will only divide a certain number of times in culture, and then they die. And younger human skin cells will divide more times than older skin cells, so it's a good research model."

As the experiments on heart function progressed, however, the team noticed that when adenosine was added to the skin cells, protein production within the cells increased and the cells grew in size.   The observation had a clear correlation with human skin health and wrinkles, given that it is well known that as people age their skin cells decrease in size and gradually lose their ability to synthesize proteins such as collagen and elastin.

Additional work by the two scientists suggested that adenosine may mitigate another age-related effect on skin- the dramatic decline in the number of capillaries supplying blood to the dermis (the connective tissue layer of the skin located below the surface.) Growth of new capillaries is dependent on the proliferation of endothelial cells which line the inside of all blood vessels. In a series of experiments, Dobson and Ethier showed that adenosine stimulated proliferation of human endothelial cells.  Results of these experiments have been presented at meetings of The American Federation for Experimental Biology and The International Symposium on Adenosine and Adenine Nucleotides- papers on this science have been published in the Mechanisms of Ageing and Development, American Journal of Physiology and Experimental Gerontology. 

In July of 2002 and in November of 2003, U.S. patents were issued to UMMS for Dobson and Ethier's technology for the application of adenosine and adenosine analogs for skin treatment.  While related patent applications were pending in territories outside of the United States, Hankook Cosmetics Company, Ltd. of Seoul, South Korea, developed an interest in the technology.

In 1999, UMMS entered into a license agreement with Hankook Cosmetics Company, Ltd., for the  exclusive development, manufacture and distribution of adenosine-based skin care products within the South Korean marketplace.

 In 2000, Hankook funded independent human studies in South Korea that showed topical application of adenosine decreased skin's propensity to stretch and reduced wrinkle depth. The company launched its first adenosine-based product line in 2001. "Their clinical data is quite impressive," Dobson said. "Many thousands of people in South Korea have used this product, and it works quite well."

To bring adenosine-based products to a broader market, UMMS signed an exclusive license agreement in July of this year with IGI  Inc. of Buena, New Jersey, developers of the patented Novasome® transdermal delivery system that encapsulates and administers therapeutic topical products.  "IGI is pleased to add adenosine to its growing portfolio which includes PTH (1-34) for the treatment of psoriasis and PTH (7-34) for alopecia," said Frank Gerardi, IGI's chairman and CEO. "We intend to use adenosine to create a new product for the treatment of skin conditions."

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The University of Massachusetts Medical School, one of the fastest growing medical schools in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. UMass Medical School and its clinical partner, UMass Memorial Health Care, attract more than $154 million in research funding annually, 80 percent of which comes from federal funding sources. Research funding enables UMMS researchers to explore human disease from the molecular level to large-scale clinical trials.



Michael Cohen