Phil Inq
Friday, October 27, 2000
Gene therapy encourages research into Parkinson's
A new treatment reversed the disease's effects in monkeys. But obstacles remain before human tests.
By Huntly Collins
INQUIRER STAFF WRITER
Scientists have used a novel gene therapy to reverse signs of Parkinson's disease in monkeys, a finding that could lead to breakthrough treatments for the debilitating neurological disorder that causes uncontrollable tremors and muscle weakness in people.
The experimental gene drug - developed by a team of American, Swiss and French scientists - makes use of a gutted AIDS virus to deliver a growth-factor gene to the part of the brain that is destroyed in Parkinson's.
The drug, which was injected directly into the brains of four aging rhesus monkeys and five young adult monkeys, prevented the brain-cell death that occurs with Parkinson's and reversed symptoms of the disease, scientists report in today's issue of the journal Science.
"It's the most potent approach I've seen," said Jeffrey H. Kordower, a neurologist at Rush Presbyterian-St. Luke's Medical Center in Chicago, who led the research team.
Since monkeys do not naturally acquire Parkinson's, the scientists artificially induced the disease by giving the younger monkeys a toxic chemical that kills the same brain cells that are destroyed in the human illness and causes the same symptoms.
Before they got the gene drug, the monkeys were so disabled they could not reach out and pick up fruit during a test of their motor skills. After the therapy, they could.
By contrast, untreated monkeys never regained their motor function.
Kordower said the therapy, if it panned out in further tests, could be a potent treatment and potential cure for a disease that afflicts between 500,000 and one million Americans, with about 50,000 cases diagnosed every year. But he said it would take three to five years to gain the regulatory approval needed to test the approach in humans - and many more years to bring any drug to the market.
Howard Hurtig, a neurologist who codirects the Parkinson's Disease and Movement Disabilities Center at Pennsylvania Hospital, said the study was impressive. He said the approach had great potential but cautioned that what worked in artificially diseased monkeys might not work in the naturally occurring disease in humans.
In an accompanying commentary in Science, Lars Olson, a neuroscientist at the Karolinska Institute in Stockholm, Sweden, said the approach provided "an optimistic outlook" for treating not just Parkinson's but also other fatal neurological disorders like Lou Gehrig's disease.
Parkinson's, described as "the saddest of diseases" by James Parkinson in 1817, involves the progressive loss of muscle control. Although people typically retain full mental capacity until the end, they have uncontrollable muscle tremors, stiffness and weakness that make it difficult to eat, wash and dress themselves.
The cause of the illness, which usually afflicts people over 60, is unknown. It occurs when certain nerve cells deep in the brain begin to die, reducing the production of dopamine, a chemical messenger that regulates muscle contractions.
The current mainstay of treatment is a drug known as L-dopa (levodopa), which replaces the lost dopamine. The treatment alleviates symptoms, but only temporarily.
Experimental approaches involve transplants of fetal nerve cells into the brains of Parkinson's victims and injections of growth-factor protein - as opposed to the gene coding for that protein - into the brain.
Neither has succeeded, and scientists turned to gene therapy as a possible alternative.
First, they removed all the genes from the human immunodeficiency virus (HIV), which causes AIDS. Without its genes, the virus cannot trigger the fatal illness, but it can act as a vehicle to shuttle genetic material into brain cells.
Then, they inserted into the HIV shell the gene that codes for a naturally occurring protein that promotes the growth and repair of the dopamine-producing cells in the brain.
Finally, the scientists used a thin needle syringe to inject these doctored viruses directly into the brains of the monkeys. The viruses entered the target cells and delivered their genetic payload, prompting the cells to churn out dopamine.
Because of potential safety concerns, Kordower said, the team is working on ways to install a chemical switch that would allow scientists to turn off the growth-factor gene in the event of side effects. Too much of the factor, for instance, could trigger psychotic illness.
That issue, he said, will have to be worked out in monkey studies before scientists proceed to human trials. |
