G-Zero receives NIAID's Phase II Small Business Innovation Research Grant

Sep 30 2011

G-Zero Therapeutics developing treatments for chemotherapy and radiation toxicity

G-Zero Therapeutics, an RTP company started in 2008 based on technologies from the University of North Carolina at Chapel Hill, has been awarded a $3 million Phase II Small Business Innovation Research Grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

The grant will fund commercialization of technology developed by UNC professor of medicine and genetics, Norman Sharpless, MD, to protect patients from cellular damage caused by radiation or cancer chemotherapy.

Sharpless, who is associate director for translational research at UNC Lineberger Comprehensive Cancer Center, leads a team that has been testing drugs to inhibit enzymes involved in cell division. His group showed that treatment with certain of these agents causes specific groups of bone marrow cells to temporarily stop dividing (which they termed 'pharmacological quiescence' or PQ-).

Scientists have demonstrated that cells which are not dividing are resistant to agents that damage DNA, like radiation and chemotherapy. Therefore, by inducing PQ- with potent and selective inhibitors of cell division, Sharpless has shown mice are protected from lethal doses of radiation and chemotherapy. Previously, Sharpless' lab has shown that the induction of PQTM even up to 20 hours after radiation exposure protects mice from a lethal dose of radiation. As opposed to existing technologies to prevent radiation or chemotherapy toxicity, PQ- protects all the normal cells of blood, including platelets, red cells and white cells.

This technology has been licensed to G-Zero Therapeutics, which will use this new funding to further commercialize these discoveries. The research was also funded by an innovation grant from the University Cancer Research Fund.

"Our goal is a simple, non-toxic pill that decreases radiation toxicity even when given after radiation exposure. We believe this approach could be of use in humans who are accidentally or intentionally exposed to lethal doses of radiation," he said.

"This funding will employ four people at G-Zero and several additional contractors in the NC research triangle region to continue to develop these experimental compounds into drugs that can be manufactured in consistent ways on a larger scale, the next step before we can apply to the Food and Drug Administration for approval to test these drugs in humans," he added.

"Dr. Sharpless and his team's groundbreaking studies were funded by a UCRF Innovation Award. The findings are both exciting and definitive, leading to UNC patents and the founding of GZero, a startup company with the goal of moving the concept into the practical arena," said Shelley Earp, MD, UNC Lineberger's director.

"The initial goals of radioprotection will be expanded by the NIH award to the advantage of people everywhere."

While radiation and chemotherapy have therapeutic uses, too much is damaging to cells. The most important acute side effect of chemotherapy or radiation poisoning is damage to the bone marrow. The bone marrow produces all the normal blood cells, and therefore a high dose of these agents can lead to low blood counts of red cells, platelets and white blood cells. Humans that receive a lethal dose of radiation as in the setting of an accidental exposure die of bone marrow failure. While there are a few drugs that will decrease toxicity when given before exposure to radiation; currently, no effective therapy exists to mitigate bone marrow toxicity of radiation when given after exposure ("radiomitigants").

Examples of applications for G-Zero's technology include unexpected radiation exposures, such as the recent Fukushima nuclear disaster that resulted from earthquakes affecting Japan. Bone marrow protection is a major issue in medical oncology, with billions of dollars spent annually in the United State alone for growth factors for this problem. In particular, PQ- protects platelets and red cells, which are largely unmet needs in current clinical oncology.

Source: University of North Carolina School of Medicine