The MDI Biological Laboratory has announced that Sandra Rieger, Ph.D., has been awarded a highly competitive grant from the National Cancer Institute, an institute of the National Institutes of Health (NIH), to study the molecular mechanisms underlying chemotherapy-induced peripheral neuropathy, a side effect of cancer chemotherapy causing symptoms such as pain, tingling, temperature sensitivity and numbness in the extremities.
The grant will allow Rieger to continue her research on peripheral neuropathy caused by Taxol (paclitaxel), a chemotherapy agent used in the treatment of ovarian, breast, lung, pancreatic and other cancers. About 60 to 70 percent of patients receiving Taxol experience peripheral neuropathy. In severe cases, patients may be forced to reduce or curtail treatment, which deprives them of cancer treatment and may decrease chances of survival.
Rieger’s research also has potential applications in the treatment of peripheral neuropathies caused by other conditions, including diabetes, aging and antibiotic treatment. Neuropathy is a general term for peripheral nerve degeneration, which is believed to affect at least 20 million Americans, with some estimates as high as 40 million. No treatments are currently available, other than for symptoms such as pain.
“This grant is an acknowledgment of the importance of Dr. Rieger’s research,” said Kevin Strange, Ph.D. president of the MDI Biological Laboratory. “Peripheral neuropathy is much more common than generally believed. Her research on the underlying molecular mechanisms of nerve regeneration opens the door to the development of new drug therapies to help the millions who suffer from this potentially debilitating condition.”
The five-year grant, which takes effect July 1, totals approximately $1.8 million over five years, with additional funding for facilities and administrative costs. The grant will fund Rieger’s continuing research in the zebrafish and research with neurologist Nathan P. Staff, M.D., Ph.D. on skin samples from breast cancer patients undergoing Taxol treatment at the Mayo Clinic in Rochester, Minn.
The research at the Mayo Clinic, which will take place over the first two years of the grant, will seek to determine if the same mechanisms that underlie Taxol-induced peripheral neuropathy in zebrafish are also linked to the condition in humans.
“The research with Dr. Staff at the Mayo Clinic is the first step to developing a drug therapy to treat peripheral neuropathy in humans,” Rieger said. “That’s my major interest — finding a therapy to cure this condition.”
The grant will allow Rieger to build on earlier research showing that Taxol-induced peripheral neuropathy is linked to the increased activity of a matrix-degrading enzyme, matrix metalloproteinase-13, or MMP-13, in the skin. The increase in MMP-13 activity leads to decreased skin resistance and the degeneration of sensory nerve endings, which in turn causes the symptoms of peripheral neuropathy.
Rieger has also discovered two compounds that prevent or reverse chemotherapy-induced peripheral neuropathy in zebrafish by inhibiting the activity of MMP-13. The compounds are the subject of a provisional patent filed last year by the MDI Biological Laboratory for their use in the treatment of chemotherapy- and diabetes-induced peripheral neuropathy. The compounds have yet to be tested in humans.
The ability offered by the grant to gain a deeper understanding of the mechanisms underlying peripheral neuropathy raises the prospect that other MMP-inhibiting drugs can be developed to treat peripheral neuropathy.