COM researcher a finalist for Cade Museum PrizeBy April Frawley Birdwell
Published: May 11th, 2012 • Category: Faculty Recognition
Since the first use of insulin in a human patient 90 years ago, one element has been a necessary part of the equation — needles. Without a needle to inject the hormone past the armor-like barrier of the skin, this life-saving medication could not enter the body, where it removes excess sugar in the blood of people with diabetes.
However, the needle’s days as a necessary evil in the management of diabetes could be numbered, based on the ideas of University of Florida College of Medicine researcher Stephen Hsu, M.D., Ph.D. Hsu, the R. Glenn Davis endowed associate professor of clinical and translational medicine and director of the college’s M.D.-Ph.D. training program, is developing an insulin patch that will deliver long-acting insulin and other large-peptide medications through the skin, without the use of needles or other technologies that break the skin’s surface.
The idea and the preliminary research it is based on, have earned him a spot in the Final Four for the final round of the Cade Museum Prize competition, named for Gatorade inventor and late College of Medicine professor Dr. Robert Cade. The winner of this prestigious $50,000 prize will be announced tonight (May 11) during the third annual Cade Museum Prize Night in Gainesville.
“When we can demonstrate bioavailability and therapeutic response using an insulin patch that is comparable to using needle injection — such a breakthrough is likely to fundamentally change the way that diabetes is treated,” said Hsu, the interim chief scientific officer for Prometheon Pharma, the company he formed to develop the patch. “There are several newer classes of injectable peptide drugs for treating diabetes that are even smaller than insulin. We eventually want to try our patch technology to deliver these and other anti-diabetic drugs. And insulin is just the tip of the iceberg. We could even create patches to replace intramuscular needle vaccination for at least some diseases, such as malaria or tuberculosis.”
Surprisingly, the idea stems from Hsu’s efforts to develop a way to topically treat precancerous cells in the cervix, a project he entered for consideration for last year’s Cade Museum Prize.
A disproportionate number of women in developing countries die from cervical cancer, often because they have no access to Pap smear screening, which provides early detection of precancerous cells in the cervix. A new test has been developed making it easier for public health workers in low-resource settings to screen for strains of human papilloma virus that are linked to the development of cervical cancer. But what was missing, Hsu thought, was a simple, accessible way to treat precancerous cells if HPV was detected, a crucial step because public health workers often must diagnose and treat women during a single visit.
Collaborating with colleagues in the colleges of Medicine, Pharmacy and Engineering, he proposed to develop a drug-containing formulation that could be delivered using a device designed like a contraceptive diaphragm. The new device would deliver chemotherapy topically to the surface of the cervix. He began testing the device in mice, which he discovered had a cervix vastly different than women.
“We were really surprised to find that the mouse cervix has a tough keratin outer barrier similar to skin,” he said.
Because the skin is such an effective barrier, only a few chemical drugs under a certain size —500 daltons in atomic weight— have been developed as patches for delivery across the skin.
“The lucrative transdermal patch industry is essentially dominated by a handful of products because even small drugs may have properties that preclude delivery across skin,” Hsu said. “But I didn’t know about these kinds of limitations.”
After teaching himself basic principles of materials science engineering, Hsu discovered a formulation that successfully delivered a medication greater than 4,200 daltons through a surface similar to skin, a discovery that sparked the idea for creating a topical patch for even larger peptide drugs such as insulin.
“We are dedicated to developing products that address urgent and unmet needs relevant to common diseases because our goal is to make a significant impact on large global populations. Hundreds of millions of people are already diagnosed with diabetes, and that will double by 2030,” Hsu said. “We want to revolutionize the way diabetes is treated. One of the effects this will have is on patient quality of life and compliance with therapy. When people hear insulin, some people don’t want to start treatment because they have needle-phobia. An insulin patch will remove this obstacle, and because it is simple to administer, compliance is expected to be higher, reducing morbidity and mortality.”
The new product also would reduce medical waste, decreasing the number of syringes and other materials thrown away after use, Hsu said.
Hsu and his team are currently focused on developing a patch for long-acting insulin, which patients with diabetes take for continuous insulin release throughout the day. They plan to test the device, called TopixDM, in a rat model of Type 1 diabetes, which occurs when the pancreas stops producing insulin, and a rat model of Type 2 diabetes, the more common form of the disease associated with obesity and insulin resistance.
The device, patented by the UF Office of Technology Licensing, also will incorporate thermal and adhesive properties so that drug formulations are solid and stable at room temperature, melt when they reach skin temperature and then stick to the skin at the site of application, Hsu said.
“Everything I want to develop uses high technology, but they are really low-tech products that are easy to use, affordable and can be used anywhere and by anyone in the world. I think that every medical advancement should try to move us closer to global health equity,” he said.
In addition to his research colleagues, Hsu has also teamed with Ly-Le Tran, M.D., J.D., serving as the company’s director of medical and regulatory affairs, and chief adviser Jamie Grooms, on the project.
This year, 120 Florida inventors applied for the Cade Museum Prize, a list that was whittled down to four after three rounds of judging by entrepreneurs, venture capitalists and technology transfer specialists. Another round of judging will occur today, where the winner will be decided.
“I could not have guessed two years ago that I would be doing anything like this,” Hsu said. “It is all serendipity.”