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Treating a Chemotherapy Side Effect Protease inhibitor developed at Georgia Tech shows promise for treating numbness in the extremities. by JANE M. SANDERS

A DRUG THAT may treat a common side effect of chemotherapy and diabetes

photo by Gary Meek Regents Professor Jim Powers and his research team are testing a compound he developed called AK295. It could be used to treat peripheral neuropathy – the condition of tingling and numbness in a person’s outer extremities. Peripheral neuropathy occurs in about 40 percent of breast cancer patients taking the chemotherapy drug Taxol. (300-dpi JPEG version - 1.04mb)

is being tested by Georgia Tech and Emory University researchers. They have found the compound, developed about a decade ago at Georgia Tech, is effective in treating neurodegenerative disease and stroke in animal models.

Researchers believe the compound, dubbed AK295, could be used to treat peripheral neuropathy – the condition of tingling and numbness in a person’s outer extremities, says its developer Jim Powers, a Regents Professor in the Georgia Tech School of Chemistry and Biochemistry. Peripheral neuropathy occurs in about 40 percent of breast cancer patients taking the chemotherapy drug Taxol. It also affects about half of diabetics.

“It’s not always clear in the early stages of testing whether a compound will be useful,” Powers says. “But we now know AK295 works in head injury and stroke models in animals.”

AK295 is an inhibitor for the calpain protease, a member of the papain family of proteases. Proteases are enzymes that cleave (basically, cut) proteins. Proteases have numerous physiological functions, including roles in digestion, blood clotting and hormone activity.

courtesy of Jim Powers These images are models of how Regents Professor Jim Powers and his research team expect their caspase inhibitors to interact with capsases enzymes. (225-dpi JPEG version - 80k)I

Proteases also have a role in metastasis in cancer, Powers notes. Some tumors secrete proteases to chew up surrounding tissue so they can expand. In breast cancer, for example, a protease called cathepsin B is present in the leading edge of invasive tumors.

Powers and collaborator Jonathan Glass at Emory University have been testing AK295 with internal funding. Now they are seeking funding to move the testing into human clinical trials, a step that may take another five years, Powers says. He and Glass have received numerous patents related to their research, and they are seeking a licensee for AK295.

In addition to AK295, Powers designs and synthesizes other small-molecule inhibitors for five classes of proteases. One of his primary research interests relates to the design and synthesis of inhibitors for cysteine proteases, which include the papain family. Papain proteases are characterized by their role in digesting proteins.

“We do a lot of computer modeling of enzymes,” Powers explains. “It is structure-based drug design.”

For more information, contact Jim Powers at 404-894-4038 or james.powers@chemistry.gatech.edu.

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Last updated: July 7, 2004