Patients with Parkinson's disease may be the first group to benefit from gene therapy, the much hyped technique that has yet to result in a single reliable treatment despite nearly two decades of experimentation. Now researchers report that a gene-bearing virus injected directly into the brain was able to improve patients' motor function without causing any adverse side effects.
In the 1990s gene therapy was hailed as an impending revolution in medicine because of its potential to attack disease at its genetic roots. The research results did not live up to the hype, however, and in 1999 much of the remaining hope for gene therapy was destroyed when an 18-year-old boy suffered an unexpectedly severe immune reaction and died during an experiment. But small-scale research continued with new safety rules in place, and studies such as this one may give the treatment option a second life.
This trial is the first time gene therapy has been tested to fight Parkinson's, which affects an estimated 500,000 Americans. The disease, which typically strikes people in their 60s, is characterized by tremors, stiffness, loss of speech and difficulty with motor function. Neuroscientists have tracked its biological cause to the death of neurons in a midbrain region called the substantia nigra, which produces the neurotransmitter dopamine. Low levels of dopamine cause the nearby subthalamic nucleus to overproduce glutamate, the brain's primary excitatory chemical messenger. The excess glutamate overstimulates other areas of the brain, disrupting motor control.
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The research team used a harmless virus to transport a gene coding for gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter that counteracts glutamate's excitation, into the nerve cells of the subthalamic nucleus. By ramping up GABA production, the gene therapy corrected the chemical imbalance and drastically improved motor function in all 12 patients. Especially significant, according to the researchers, is that this improvement persisted even when the patients were taking their Parkinson's drugs—meaning the two treatments could be combined for extra impact.
“The safety and effectiveness clearly indicate that this is something worth pursuing,” says lead author Michael Kaplitt, a neurological surgeon at New York–Presbyterian Hospital/Weill Cornell Medical Center. “But we still need to do a larger, more definitive study to prove this for sure.” Kaplitt hopes to have a large-scale trial under way by the end of the year.