New research into gene therapy has paid off with the first successful effort seen yet to fight cancer as well as two early-stage trials that point to a new method for treating Parkinson's disease. Last month, a team of scientists at the National Cancer Institute (NCI) in Bethesda revealed that they had successfully treated two out of 17 patients with advanced metastatic skin cancer using gene therapy techniques that modified their own immune cells. "These results represent the first time gene therapy has been used successfully to treat cancer," said NIH director, Dr. Elias A. Zerhouni. And he's hoping that the work is applicable not only to melanoma, "but also for a broad range of common cancers, such as breast and lung cancer." The process is by no means foolproof. Fifteen of 17 patients in the study continued to fight malignant melanoma, with only two free of cancer after 18 months of therapy. Doctors caution that a considerable amount of work remains to refine the procedure and fully test its safety. But the survival of the two cancer-free victims was solid proof that gene therapy can work — even for patients given only a three to six month prognosis. A team of researchers at the NCI led by Dr. Steven Rosenberg concentrated on altering lymphocytes, or white blood cells. Scientists isolated the patients' potent immune T cells and multiplied them in a lab. A virus was then used to transport receptor genes to the T cells, modifying them to recognize specific melanoma cells, pursue them and kill them. The T cells were then infused back into the patient, a population of cells that made up at least 10 percent of all the T cells in the patients' bodies for two months. And the researchers say they're working to lengthen the life of the specially modified T cells to make the therapy more effective. In one case, the therapy not only rid the patient of skin cancer, it also reduced a tumor on a lung to the point surgeons were able to remove it. The NCI is now treating advanced melanoma patients using adoptive transfer of genetically altered lymphocytes, said Rosenberg, "and we have now expressed other lymphocyte receptors that recognize breast, lung, and other cancers." "These successes in treating advanced melanoma bring hope that this type of gene therapy, altering lymphocytes, could be used in many types of common cancers and could be achievable in the near future," said acting NCI director Dr. John E. Niederhuber. Once under a cloud over safety issues, gene therapy has been making a comeback in the research world. Trials were halted in 1999 and again in 2005 after patients died in trials. In the most recent case, three French children developed leukemia during gene therapy trials for inherited immunodeficiency diseases. But recently, successes have outnumbered failures. Following the cancer trial, two different research teams announced that they had successfully used gene therapy techniques to treat Parkinson's disease. In one case, a virus was modified with a gene for an enzyme which produces the neurotransmitter GABA. All 12 patients in that study demonstrated significant improvements in disease symptoms of at least 25 percent while nine improved at least 37 percent and five demonstrated gains of 40 percent to 65 percent. All benefits persisted for a minimum of one year. In a separate trial at the University of California, San Francisco, researchers used a gene modified by the growth factor neurturin, which some studies indicate plays a role in slowing the loss of vital dopamine-producing cells. A group of 12 Parkinson's patients were given two doses of the therapy, CERE-120, with the low-dose group recording a 40 percent improvement in symptoms — a reduction of the time when normal Parkinson's medication was ineffective and symptoms were troubling to the patient — and the high-dose group demonstrating a 50 percent improvement. CERE-120 is being advanced by San Diego-based Ceregene, which is also pursuing gene therapy for Alzheimer's and ALS. "Based on … the intriguing efficacy observations, we're eager to continue to support research in phase II that will more definitively assess the potential of CERE-120 to treat PD," said Deborah W. Brooks, president and CEO of The Michael J. Fox Foundation. "It's very encouraging that two companies were able to show benefits with no significant adverse effects," Katie Hood, the Foundation's deputy CEO said. "Safety is obviously the first hurdle." December 2006