Researchers at the Indiana University School of Medicine report that the anti-cancer drug Gleevec holds out promise to become the first effective treatment for neurofibromatosis, a genetic disease that has resisted treatments until now.
The research team is conducting clinical tests of the drug following successful laboratory tests and a "compassionate use" of the drug that showed dramatic results in a three-year-old girl at Riley Hospital for Children in Indianapolis.
Neurofibromatosis results from mutations in a gene called NF1, which causes tumors to form in the cells that make up the protective sheaths around nerves. In humans, NF1 mutations resulting in neurofibromatosis occur in one in 3,500 births, equally affecting both sexes and all races and ethnicities. It is the most common genetic disease in humans that results in a predisposition to cancer.
IU researchers have begun a phase 2 clinical test of Gleevec, treating neurofibromatosis patients with plexiform neurofibromas, which affect about 40 percent of people with neurofibromatosis. Such tumors often have a severe impact on patients' quality of life and can be fatal. They do not respond to chemotherapy drugs and are difficult or impossible to remove surgically.
"We are very hopeful about the potential of this drug and related therapies. There are no other therapies for these tumors. These patients often suffer for years; they sometimes die from these tumors. These are very slow growing tumors that impair people's everyday lives," said D. Wade Clapp, M.D., Freida and Albrecht Kipp Professor of Pediatrics at the IU School of Medicine.
The researchers report in the Oct. 31 issue of the journal Cell that the mutated nervous system cells, while still in a pre-tumor state, use molecular signals to recruit inflammatory system cells from the bone marrow to the vicinity of the nerve cells. Those inflammatory system cells - called mast cells - then are put to work helping create the cellular "scaffolding" and blood vessels necessary for the cancerous tumors to form.
The tumorigenic cells use a signaling system protein called c-kit to recruit the mast cells, making Gleevec an attractive treatment candidate because it acts on the c-kit molecule, said the researchers, who include Feng-Chun Yang, M.D., Ph.D., assistant professor of pediatrics, David A. Ingram Jr., M.D., associate professor of pediatrics, and Luis F. Parada, Ph.D., professor of developmental biology at the University of Texas Southwestern Medical Center.