Walter Liskiewicz, an oral surgeon in Jackson, Mich., was 44 when he lost control of his body to Parkinson's disease. Fading signals from nerves dying deep inside his brain left his hands rigid and trembling and quickly forced him into early retirement. He found solace in music, writing and producing smooth jazz under the name Waldino. But within 10 years, he could barely move.
"Up to 70 percent of the time, I couldn't do anything," Liskiewicz, now 60, said. "I would sit in a chair."
Parkinson's disease disrupts a complex brain circuit that controls movement, making voluntary actions nearly impossible to initiate and involuntary ones impossible to control. Drugs that boost the effects of dopamine -- the neurotransmitter released by the degenerating neurons -- can help reduce the symptoms. The effects, however, gradually wear off and the side effects can become equally debilitating.
But the promising results of a gene-therapy trial have offered new hope to people with Parkinson's disease. The controversial approach uses virus particles to infuse new genes into a patient's own cells.
"This opens up the field of genetic medicine and brings us dramatically closer to it being a reality than ever before," said Dr. Michael Kaplitt, associate professor of neurological surgery at Weill Cornell Medical College in New York City and senior author of a report on the trial's results published in the Lancet Neurology.
Parkinson's disease affects roughly 500,000 people in the United States, making it the second-most common neurodegenerative disease after Alzheimer's. Drugs are the first line of treatment, followed by deep-brain stimulation, a procedure that implants electrodes deep into the brain to "hotwire" the damaged circuit.
Liskiewicz came across the clinical trial online one night.
"I asked my doctor about it and he said he had just applied to be one of the trial sites," Liskiewicz said. "I said, 'Make me No. 1 one on your list.'"
The goal of the therapy is to provide patients' cells with the blueprints to make proteins that have a therapeutic effect. In this case, the blueprint encoded an enzyme called GAD that would act like a chemical form of deep-brain stimulation, avoiding the need for electrodes, wires and battery packs.
"This procedure promised to provide the same things without all the hardware, and that was appealing," Liskiewicz said.
"Part of the reason we do research is to continue to offer patients new options," Weill Cornell's Kaplitt said.
Compared to deep-brain stimulation, gene therapy involves less hardware, less maintenance and fewer procedures, making it more cost effective and limiting the risk of infection, Kaplitt said.
But the experimental treatment comes with risks. The death of Jesse Gelsinger, 18, who joined a clinical trial for a rare liver disease in 1999 cast a shadow on gene therapy in the United States. The approach has the potential to provoke an immune response (the effect implicated in Gelsinger's death), cause unwanted changes in surrounding normal cells and irreversibly change the patient's DNA in ways that could potentially lead to cancer.