Aug. 6, 2009 — Power plants produce energy by burning coal. Human beings burn a compound called adenosine triphosphate, or ATP for short. And while power companies struggle to find ways to deal with the byproducts of combustion, evolution solved that problem for humans long ago. The human body not only recycles the byproducts of ATP, it has found other uses for them as well.

One of these molecules – adenosine – is produced when cells under stress burn lots of ATP. Accordingly, it has been adapted by the body as a cell-signaling agent, to help the body deal with inflammation and injury. Because receptors for adenosine are found on virtually every cell type in the body, its therapeutic potential for treating diseases like diabetes, atherosclerosis and arthritis is vast.

For more than 40 years, researchers at the University of Virginia have been world leaders in uncovering adenosine's role in cell signaling and in synthesizing molecules similar to adenosine. Realizing that this research had the potential to significantly improve human health, Joel Linden, a professor of cardiovascular medicine, and Timothy Macdonald, professor of chemistry, joined forces with business executive Robert Capon to build a company that licensed U.Va. patents in this area.

Their work has shown such promise that their company, Adenosine Therapeutics, was bought in 2008 by Clinical Data, a global pharmaceutical company, in one of the largest deals of its type ever done with University technology.

The key to harnessing adenosine has been the identification of the four adenosine receptors, each of which sets in motion a specific cascade of events within the cell when adenosine docks with it. Linden played a prominent role in identifying these receptors, and his collaboration with Macdonald enabled him to elucidate the functions of each one. Macdonald synthesized adenosine-like molecules that would dock with a specific adenosine receptor, either mimicking the action of adenosine or blocking it.

In effect, these molecules allowed Linden to turn the receptors on and off, the key to enabling him to discover their function.

"When you're doing biological research, the University's tradition of medicinal chemistry is wonderful," Linden said. "You can walk across campus and find people who can help you develop the research tools you need as well as create potentially therapeutic drug candidates."

Linden found that one of the four receptors is responsible for dilating coronary arteries. The ability to dilate these arteries at will is particularly useful for imaging coronary arteries in the hearts of people who are not healthy enough to undergo traditional treadmill stress testing.

Although there are other pharmacological stress agents on the market, Macdonald's synthetic vasodilator potentially causes fewer side effects, is fast-acting and disappears from the system quickly. Adenosine Therapeutics has shepherded this compound, named StedivazeTM, through development. It will enter Phase III clinical trials later this year, where it will be evaluated against existing treatments.

Additional compounds are in development to treat a variety of inflammatory diseases. Both Linden and Macdonald have received the Edlich-Henderson Inventor of the Year Award from the U.Va. Patent Foundation for their discoveries.

Adenosine Therapeutics served to amplify the consequences of Linden's and Macdonald's work in other ways. Researchers in fields like nephrology, infectious disease and transplantation who were intrigued by adenosine's ability to control inflammation partnered with Adenosine Therapeutics to secure federal Small Business Innovation Research grants. These grants are meant to help commercialize research discoveries, and the company's role was to supply the specialized molecules these researchers needed.

"This process brought in tens of millions of dollars in research funding to the University," Linden said. "In the process, researchers could assemble the preliminary findings they needed to apply for traditional NIH grants for more basic research."

The result of this work has been more than a score of patents held by the University for uses of adenosine-related compounds. Many of these patents were paid for, licensed, improved, and commercialized by Adenosine Therapeutics.

"All this activity benefits the University because it adds to the stock of intellectual property it holds and creates value by developing its patents into commercial products," Capon said.

By raising private equity capital and through its relationships with larger pharmaceutical companies, Adenosine Therapeutics secured the funding needed to finance clinical trials, moving these inventions closer to commercialization, where they can potentially bring benefits to patients by fulfilling important unmet medical needs.

"This is a great tribute to the University," Capon added.

"The benefits of a company like Adenosine Therapeutics are broader and deeper than most people realize," Linden said. "A company is an engine that expands the research and development capability of the whole institution. Research at the company and research at the University are synergistic. As long as U.Va. maintains its prominence in medicinal chemistry there will be opportunities for new start-up companies like Adenosine Therapeutics."