On a steamy day in August, doctors at Weill Cornell Medical College in New York City injected virus particles, laden with a gene to dampen overwrought neurons, deep into Nathan Klein's brain. The aim: to rid him of Parkinson disease.

Drill-happy: Experts have criticized the injection of virus particles directly into the brain. Credit: Weill Medical College

The trial may seem bold, but it is only the latest in a series of seemingly drastic schemes cooked up to treat the disorder. Implanted electrodes that zap brain cells, a drip feed of nutrients to keep the cells alive, even transplants of aborted fetal tissue have all found their way into human guinea pigs with Parkinson disease.

One obvious reason therapies for the disease are so aggressively pursued, say experts, is the fierce demand from patients: an estimated 4 million people worldwide suffer from the disease. The standard treatment, the drug levodopa, proves insufficient over time and causes severe side effects. The call for effective treatments has also been fuelled by the advocacy of celebrity patient Michael J. Fox.

That aside, the disorder is a good practice ground for therapies because its underlying brain chemistry is well defined. A group of neurons that make the neurotransmitter dopamine withers, affecting the circuits that control movement. In contrast, the molecules underlying Alzheimer disease—which affects the entire brain—are only just being unraveled.

Based on the well-mapped circuits in Parkinson disease, researchers have been able to precisely target their interventions. One technique, deep brain stimulation, emerged from the surgical practice of slicing offending areas such as the subthalamic nucleus. Doctors have now helped thousands of patients by implanting electrodes that shock the same spots, though they remain unsure how it works.

Good animal models, as well as the ability to measure disease progression, have also pushed therapies from lab bench to clinic. In a study published in March (Nat. Med. 9, 589–595; 2003), a UK-based team monitored the symptoms of five people who had glial cell line–derived neurotrophic factor pumped into their brains through their skulls. The protein rejuvenates dopamine-making neurons and has stalled patients' decline by two years, claims team member Clive Svendsen of the University of Wisconsin, Madison.

Other techniques have stirred more controversy. In trials reported in 2001 and August of this year, transplants of nerve tissue from aborted fetuses did little to improve patients' symptoms, and left some with involuntary movements called dyskinesias. But many researchers remain confident that the teething troubles can be ironed out, perhaps by grafting lab-grown stem cells. “I'm a strong believer in cell transplantation,” says Patrik Brundin of the Wallenberg Neuroscience Center in Sweden.

Although most new techniques receive cautious support from the research community, the recent gene therapy trial, which will be extended to 12 patients, has drawn fierce condemnation. Critics worry that the trial proceeded into humans despite insufficient experiments in animals, and that the infused virus might spread to other organs. “I don't think it should have gone ahead,” says neurologist Anthony Lang of the University of Toronto.

Whatever their outcome, these techniques might fall by the wayside if researchers can discover what causes dopamine-making cells to die. Says Warren Olanow of Mount Sinai Medical School in New York, “If I had to pick one [approach], it would be understanding the etiology.”