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New Treatment Promising for Parkinson's
New York, NY - Jun 22 2007
An experimental treatment for Parkinson's disease seemed to improve symptoms - dramatically so, for one 59-year-old man - without causing side effects in an early study of a dozen patients.
The gene therapy treatment involved slipping billions of copies of a gene into the brain to calm overactive brain circuitry.
The small study focused on testing the safety of the procedure rather than its effectiveness, and experts cautioned it's too soon to draw conclusions about how well it works. But they called the results promising and said the approach merits further studies.
"We still have quite a bit more testing to do," said Dr. Michael Kaplitt of Weill Cornell Medical College in New York, an author of the study. Still, "the initial results are extremely encouraging."
Kaplitt and collaborators report their results in this week's issue of the British medical journal, The Lancet.
They're not alone in trying gene therapy for Parkinson's. In April, another team told a medical meeting that its experiments, which delivered a different kind of gene to a different part of the brain, also appeared safe and gave a preliminary hint of benefit.
More than half a million Americans have Parkinson's. They endure symptoms that include tremors, rigidity in their limbs, slowness of movement and impaired balance and coordination. Eventually they can become severely disabled.
Nathan Klein, a 59-year-old freelance television producer in Port Washington, N.Y., said the disease left him "pretty messed up." It weakened his voice, impaired his walking and made his hand tremble so badly he couldn't hold a glass of wine without spilling it all.
Klein was the first patient to be treated with Kaplitt's gene therapy procedure in 2003, and he said his symptoms gradually subsided afterward. Nowadays, he said, apart from freezing now and then when he wants to walk, the symptoms are basically gone.
"I'm elated," said Klein, who continues to take his regular pills for the disease. "It's unbelievable."
Kaplitt, who has a financial interest in Neurologix Inc., which paid for the research, noted that the 12 patients in the study still have Parkinson's symptoms. The amount of medication they were already taking for their symptoms didn't change significantly in the year after the surgery.
Current medicines can control symptoms, but can't stop the disease from getting worse over time, and they can produce troublesome side effects like uncontrollable movement.
Some patients gain relief from a surgical treatment called deep brain stimulation, in which electrodes are placed in the brain and connected to a programmable stimulator. Kaplitt's procedure was aimed at achieving the same goal as that surgery, calming overactive circuitry in the brain. It gets overactive because it loses the normal supply of a chemical called GABA. The gene therapy was designed to make the brain produce more GABA.
For the gene therapy surgery, a tube about the width of a hair was threaded through a hole about the size of a quarter at the top of the skull. The tube delivered a dose of a virus engineered to ferry copies of a gene into cells of a brain region called the subthalamic nucleus. The gene copies enable the cells to pump out more GABA.
The Lancet paper reports that over a year, patients showed no side effects from the procedure. What's more, they showed improvements in an overall assessment of symptoms like tremors, stiffness and walking problems.
The improvements were evident at a checkup three months after the procedure and persisted to the end of the study, one year after the surgery, researchers reported. By that time, the overall amount of improvement from before surgery was about 24 percent when measured at times that patients were off their normal medication, and 27 percent at times when they were on medication.
Most of the effect appeared on just one side of the body. Because of concerns about safety with the untested procedure, the researchers treated only the brain circuitry controlling one side of the body.
Dr. Karl Kieburtz of the University of Rochester Medical Center, who didn't participate in Kaplitt's work, said the lack of any apparent side effects is itself significant.
But he urged caution in interpreting the evidence of benefits in symptoms. Other experimental therapies that looked good at such a preliminary stage have failed to pan out in more rigorous studies, he said, so more research is needed.
Future studies could include a head-to-head test against deep brain stimulation to see which relieves symptoms better, said neurosurgeon Dr. Guy M. McKhann of the Columbia University Medical Center in New York.
Dr. J. Timothy Greenamyre of the University of Pittsburgh, who was also familiar with the results, said the new study and prior research in animals leave him "very optimistic" about Kaplitt's approach.
Source: The Associated Press
Commentary from the Parkinson's Disease Foundation
New Gene Therapy for Parkinson's Disease
Kaplitt and colleagues reported in Lancet (2007;369:2097-2105) the one year results of their study of 12 patients with Parkinson's disease who received a gene implantation for a brain protein, termed gluatmic acid decarboxylase (GAD) attached to a viral vector. This treatment involved a neurosurgical procedure in order to implant the genetic material into a deep brain region known as the subthalamic nucleus. The scientific premise of this treatment is based on the knowledge that there is a reduced input of the neurochemical, gamma-aminor-butyric acid (GABA) to this region in Parkinson's disease and the treatment is aimed at increasing GABA activity. The surgical treatment placed the genetic material through small needles in one subthalamic nucleus. The study was "open-label", meaning that all patients and all staff involved in the program knew that each patient received the treatment. The aim of the study was to demonstrate safety of the treatment over 12 months. The researches found that the treatment was safe and no patient developed significant adverse events related to the new gene therapy. Improvement occurs in parkinsonian signs, and special neuroimaging studies to measure brain chemical activity (positive emission tomography or PET scans) showed evidence of the anticipated reduction in metabolism within the thalamus, another brain region involved in the subthalamic network of nerve fibers. The changes occured only on the side of the surgery.
The study is important because it is the first step in testing this new gene therapy technique , and at least within the first year, the treatment is safe. The improvements in parkinsonism and the PET scan results are encouraging, but further long-term follow-up in these patients and larger "double-blind" studies where some patients receive treatment and others do not are needed to verify the initial findings.
Gene therapy is a novel treatment that is being explored in Parkinson's disease and other neurological disorders. Currently, another gene product, neurturin, is being tested and has already proceeded from the initial "open-label" phase to the "double-blind" phase in Parkinson's disease. Advances in gene therapy offer the possibility to change the fundamental biochemical and cellular activity of the brain on a long-term basis.
Christopher G. Goetz, M.D. Chair, PDF Medical Policy Subcommittee
Source Date: Jun 22 2007
Source Publication: The Associated Press