By Paul Glader
14 October 2002
The Wall Street Journal Europe
(Copyright (c) 2002, Dow Jones & Company, Inc.)
The first clinical trials of gene therapy to treat patients with Parkinson’s disease are expected to be under way in the U.S. by the end of this year — on the heels of new fears about using genes to treat diseases.
The researchers, who will conduct the Parkinson’s trials at New York Presbyterian Hospital/Weill Medical College of Cornell University, have a go-ahead from the Recombinant DNA Advisory Committee — a U.S. National Institutes of Health review panel that oversees gene-therapy trials — as well as approval from the U.S. Food and Drug Administration.
That approval came before news earlier this month that scientists in France and the U.S. had suspended studies of a gene-therapy approach that appears to cure a rare immune disorder dubbed “bubble-boy disease,” after a French patient developed a leukemia-like condition.
At a special FDA meeting Thursday called to discuss the boy’s illness, government advisers agreed that the gene therapy probably made the French boy ill but said the risks weren’t high enough to justify stopping the experiments for children with the often-fatal disease. They also urged that parents and patients be warned about the risk of retroviruses — the kind used in the French toddler’s case. The concerns are reminiscent of the regulatory scrutiny and soul-searching that followed the death of 18-year-old Jesse Gelsinger in a 1999 gene-therapy trial at the University of Pennsylvania.
The Parkinson’s researchers say they believe their trial will be safe. They have revised their clinical models and safety protocol several times, once at the request of the influential NIH review panel. They have conducted five sets of tests in rats and a safety test in seven primates. In a paper published Friday in the journal Science, they said the genes, inserted into viruses and injected into rats, appeared to slow the progression of the disease.
Still, the researchers know they are venturing into a controversial area. When they sought clearance from the NIH committee, “people openly expressed surprise that this idea came to the panel,” said Michael Kaplitt, one of the Weill researchers.
More than 10 million people world-wide, including 1.5 million Americans, are estimated to suffer from Parkinson’s disease, a degenerative neurological disorder that causes impaired movement and other symptoms. Researchers believe Parkinson’s is caused when nerve cells that produce the brain chemical dopamine degenerate. The loss of dopamine causes a terrible cascade of neural events, centering in the subthalamic nucleus region and leading to an inability to control body movements. Patients suffer a progressive loss of motor functions, experiencing trembling, rigid muscles, slowed motion and a loss of facial expression.
Scientists are investigating numerous possible causes and cures for the disease, which research is showing may develop through environmental or genetic causes, depending on the type. One of the most widely used surgical treatments for Parkinson’s is the deep-brain stimulation technique, which involves inserting an electronic probe into the brain to quiet the subthalamic-nucleus region.
“Stimulation works but still has its downsides,” said Dr. Kaplitt. “There is lots of hardware on the body,” he adds, referring to electrodes and batteries among other stimulation necessities.
Dr. Kaplitt and a senior research partner, Matthew During of the University of Auckland in New Zealand, hope the gene-therapy technique will provide a better alternative to deep-brain stimulation. The gene-therapy surgery involves inserting the GAD (for glutamic acid decarboxylase) gene into a nonpathogenic class of viruses, called the adeno-associated virus, or AAV. The injected virus delivers the gene into cells in the affected area of the brain.
The GAD gene produces a brain chemical called GABA, which is released by nerve cells to calm them down. The therapy works on the nerve cells in the subthalamic nucleus region that have become overactive due to a lack of dopamine.