Two University of Massachusetts Medical School researchers were studying how aging affects heart function. They were particularly interested in adenosine, a naturally occurring molecule that helps both heart muscle and blood vessel walls contract and relax. Cardiologists use the substance to restore normal heart rhythm or to dilate blood vessels when they want to run diagnostic imaging tests.
The best way for the pair of scientists to look at adenosine was to
watch how it behaved in cells cultured in a laboratory dish. That
would be a more controlled environment than inside the heart, where
blood is circulating with hormones and other substances that would
muddy the picture of how adenosine affects cellular processes.
So the two colleagues, Dr. James G. Dobson Jr., professor of physiology and medicine, and Dr. Michael F. Ethier, assistant professor of medicine, set to work on human skin fibroblasts, a common kind of cell culture. They grow for 40 or 50 cell division cycles over the course of months, providing a scientific model of the aging process.
Drs. Dobson and Ethier can be forgiven for initially ignoring the change they saw on the functional equivalent of a painter’s blank canvas. What they eventually noticed was how the skin cells they were observing responded to adenosine in ways that related to skin health and the wrinkles that come with aging.
“I vividly remember the revelation in the office,” Dr. Dobson said. “It was serendipitous.”
He and Dr. Ethier, whose work now focuses on adenosine and asthma, consider themselves basic researchers far removed from the world of wrinkle creams and cosmetic counters. But what they discovered about adenosine’s potential to enhance skin condition led to a patent later licensed by two companies for use in the beauty industry.
In 1999, a South Korean company called Hankook Cosmetics Co. Ltd. licensed the intellectual property and two years later, after conducting its own human testing, launched a product line based on adenosine’s ability to reduce skin stretching and wrinkle depth. In July a second company, IGI Inc. of Buena, N.J., bought licensing rights outside South Korea. IGI is not a cosmetics company, but works with cosmetics and pharmaceutical companies to improve how products like an adenosine-based skin cream are applied to the skin. Two examples are remedies for psoriasis and hair loss during chemotherapy.
Drs. Dobson and Ethier discovered that adenosine caused three important things to happen in skin cells. First, adenosine boosted the production of collagen and elastin, two proteins in skin cells that gradually diminish as people age.
“When we found it increases protein synthesis in cells, that’s when we started talking about the effects on skin,” Dr. Ethier said.
Second, adenosine caused skin cells to become bigger, another quality associated with young skin.
“We had found these cells decrease in size with age,” Dr. Ethier said.
“We’ve got something here that works against the aging process.”
Third, adenosine stimulated the proliferation of endothelial cells,
which line the inside of blood vessels. These cells are precursors to
angiogenesis, which begins with the growth of capillaries that carry
blood to the dermis, the layer of connective tissue below the surface
of the skin.
“We knew in aging, the blood supply decreases dramatically,” Dr. Ethier said.
That makes the skin get thinner, because it doesn’t get as many nutrients.
“Adenosine has what appears to be multiple beneficial effects on the dermis,” or layer of connective tissue below the skin’s surface, Dr. Ethier said.
The action of adenosine on human endothelial cells and angiogenesis had been reported by the two researchers in the American Journal of Physiology. But there have been no clinical trials of adenosine’s effects as a topical skin treatment.
“We were considering doing human studies, but we realized that’s not our expertise,” said Dr. Ethier. “We’re basic scientists.”
Without clinical trials on humans, the effects of adenosine are hard to evaluate, said Dr. Nelson Lee Novick, clinical professor of dermatology, at the Mount Sinai School of Medicine in New York and one of two American Academy of Dermatology members with expertise on cosmetic ingredients who said last week that they could not comment on the products to come out of the UMass research labs.
“Of all the currently available topical anti-aging preparations, tretinoin, the active ingredient in the prescription products Retin A and Renova, remains the most extensively studied and has been demonstrated to diminish fine wrinkling after several weeks of appropriate use,” Dr. Novick said in an e-mail response to an interview request. He has no financial or other interest in Retin A, Renova or any other product.
In 1999, the two UMass scientists took their data to the medical school’s office of technology management, which explored opportunities to capitalize on their work. Unlike the biotech industry, which typically trolls scientific journals or meetings looking for partnerships to strike with universities, the cosmetic market took some searching by the UMass office, said Chester A. Bisbee, acting executive director. The agreements with Hankook and IGI are the only ones UMass Medical School has with companies in the cosmetic industry.
The licensing deal with IGI is one of the top five licenses the medical school has. Its program pulled in just over $26 million in gross licensing revenue for the fiscal year that ended in June, $19 million of which was generated by products coming from the Massachusetts Biologic Laboratory in Jamaica Plain, which became part of UMass in 1997. The leader in license revenue is Synagis, a vaccine for the childhood illness respiratory syncytial virus, or RSV, that is sold by MedImmune Inc. Hopes are high for future products based on RNA interference, a gene-silencing mechanism that is the focus of many researchers at UMass Medical School.
“All universities look for the blockbuster. Most universities want to win the lottery and most bigger programs do in fact win the lottery at some point,” Mr. Bisbee said. “This is not our multimillion-dollar hit, but one would not expect that for a cosmetic product.”
Mr. Bisbee places the adenosine licensing revenues in “the high six figures, $500,000 or $600,000 to a million.” The money is typically split between the investigators, their departments and the institution, with 10 percent off the top to support the technology transfer office. UMass Medical School retains ownership of the patents involved.
“UMass has a variety of things we hope will be big hits,” he said. “Only time will tell. Some have not turned out to be what we thought and some have turned out to be more than we thought. That’s the lottery aspect.”
While the skin products continue to be sold in South Korea under the Ossion brand name as skin care creams to be used in stages over eight weeks, it will take IGI a year or more to develop and test its method for making adenosine easy to use, said Frank P. Gerardi, IGI’s chairman and chief executive officer. He described his company’s mission as licensing drugs and technology from universities to see if its delivery system would enhance efficacy.
IGI’s patented delivery system, called Novasome, offers four advantages, he said.
“We believe we can improve the application of adenosine by giving it the qualities of delayed release over eight to 10 hours, deep penetration to the dermis, non-irritation and stability of the product,” he said.
IGI is in talks with another company to test the skin cream on humans.
Dr. Dobson hopes that adenosine might one day also be used therapeutically to help make older skin healthier. Adenosine is safe, he said, because it is a naturally occurring molecule already approved as a heart drug that is quickly metabolized by the body. Allergic reactions are unlikely because it is not a protein, which usually is the culprit in bad reactions.
For now the researchers await IGI’s work to launch the skin cream in the United States.
Dr. Ethier remembers bringing home a South Korean vial of Ossion skin cream.
“When I showed it to my wife and daughter, I just looked for the adenosine content,” he said. “But they knew what to do with it.”