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How Phony Heroin Led to Deep Brain Stimulation, a Choice Treatment for Parkinsonís

by Gopalan on  September 22, 2007 at 11:36 AM Research News   - G J E 4
How Phony Heroin Led to Deep Brain Stimulation, a Choice Treatment for Parkinsonís
Toby Govea used to shake violently and uncontrollably 25 years ago. An inmate of In Monterey County Jail, in California, had developed symptoms of Parkinson's Disease.
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Today, Govea remains incarcerated -- but free of tremors, thanks to a treatment made possible by research on the prisoner's own brain.

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The treatment, called deep brain stimulation, has become the leading surgical treatment for Parkinson's, which afflicts 1.5 million Americans. It has been performed on more than 20,000 patients in the past decade.

In July of this year at the Atascadero State Hospital in California, Govea was lucid, and his muscles were still, as he recalled the events that made him a human guinea pig who helped develop a treatment for his own illness.

He had learned drug use from his family as a kid, experimenting with cocaine, PCP (phencyclidine), illicitly marketed drug under a number of street names including Angel Dust, Supergrass, Killer Weed, Embalming Fluid, and Rocket Fuel.

Before long he became before becoming a heroin addict. And then he fell victim to MPTP, a synthetic narcotic. Typically, it's a discarded byproduct of heroin synthesis.

And his limbs began to shake, one after another. "This leg, then this arm, then this leg," Govea said. "Then I shot some more and this arm started." In less than two weeks he had given himself symptoms of advanced Parkinson's disease. Shortly after that, he was arrested for petty theft and sent to Monterey County Jail.

When he was released, his mother took him to several doctors who were baffled by his case. They diagnosed Govea with an unusual form of Parkinson's disease, but they did not know, because he would not tell them, that his shaking had begun after dosing repeatedly with MPTP, a phony heroin.

Finally, Santa Clara Valley Medical Center doctors recognized his symptoms. They had seen a handful of similar cases, all caused by accidental dosing with MPTP. By figuring out that heroin use was the one thing Govea had in common with the other patients, the doctors linked his condition with intravenous MPTP injection.

The knowledge opened a window to the inner workings of Parkinson's disease that changed the prospects of people suffering from it -- including Govea -- overnight.

The Santa Clara doctors published their research in the journal Science.

What MPTP did to Govea's brain is very similar to what happens in the brain of a person with Parkinson's disease. The chemical had eaten away the normal, dark-colored cells in a small area at the base of the brain called the substantia nigra (Latin for "black stuff") -- which is also damaged by Parkinson's disease.

These cells normally produce dopamine, a neurotransmitter that allows brain cells to communicate with one another. Their dead area in Govea's brain resulted in the abrupt onset of the symptoms of Parkinson's disease: slowness, rigidity and tremor.

To researchers, a chemical that essentially induces Parkinson's is like a golden egg: rarely discovered and very valuable. Researchers could suddenly create an animal model of the disease, which provided unprecedented insights into new treatments. Deep brain stimulation eventually evolved out of the physiological and neuroanatomical understanding derived from studies performed with MPTP in animals.

But as the research was still ongoing, Govea's condition worsened. He became emaciated and unable to eat, drink or use the bathroom by himself. His mother had taken to feeding him through a straw. "I'm tired of shaking," he told her, "If I die, let me die."

In August of 1981, he found brief respite. He was treated with a drug called levadopa, and his symptoms virtually vanished. But the medication caused hallucinations and delusions -- side effects worse than the symptoms it was meant to treat. Govea blamed the "voices in his head" in 1982 when he was nabbed for a bank robbery in Greenfield, California. Several customers had recognized him by his tremor. He spent the next decade in Vacaville State Prison.

In 1991, about 90 days after his release, he said he began hearing voices again. They told Govea to rob a liquor store at knifepoint, which he did. He was sent back to prison and in 1995 at Pelican Bay State Prison, he attacked a guard and was charged with attempted murder. He pleaded not guilty by reason of insanity and was sentenced to a minimum of 31 years at Atascadero State Hospital, a term he now serves.

"He did not do well when he first came," said David Curtis, his former social worker. He was extremely violent, assaulting patients and hospital employees. On top of that, by the late '90s another side effect of levadopa called dyskinesias, involuntary jerking and swaying movements, had become so bad that it occasionally cut off his breathing.

In 2001, in a last-ditch effort to help Govea, the doctor assigned to the hospital's medical unit, Dr. Linda Kocsis, asked him if he would be willing to undergo an experimental procedure, called deep brain stimulation, to treat his tremor. Govea said she told him: "You'd be like a guinea pig."

When Govea underwent the procedure in 2003, a small hole was drilled in his skull, and an electrical wire -- about the thickness of a strand of spaghetti -- was inserted into a small area called the subthalamic nucleus, part of the complex basal-ganglia system associated with steady muscle control. The wire was then connected to a battery pack, which generates a pulsing electrical current. Doctors implanted the battery in his abdomen in a separate operation (it's now typically placed under the collar bone).

The electrical stimulation alleviates the symptoms of Parkinson's disease, though no one knows exactly how. The most basic answer is that deep brain stimulation is setting up an interference pattern for abnormal electrical activity in the brain. "Like a jamming mechanism," Christine said.

Electrical firing patterns are abnormal in patients with Parkinson's disease. The subthalamic nucleus is firing too frequently, and its pattern is erratic, causing the motor system to go on the fritz. Deep brain stimulation could either be interfering with this activity or, alternatively, "reasserting a more normal rhythm to this part of the brain ... a more normal firing pattern," Christine explained. Some scientists think the data indicate that its effects are even better than that. To meet Govea is to see why.

Four years after his surgery, Govea's symptoms are still under control. "Look at my hand," he said, holding it perfectly still. He takes his own pills now, and he can read the newspaper without tearing it apart. Deep brain stimulation has "just changed my whole life," he said.

That's the irony of Govea's story. Advancements in the understanding of Parkinson's disease were made possible by the discovery of MPTP, which was made possible by Govea's fateful dosing with the drug. It also led to the development of deep brain stimulation. In essence, Govea has received a treatment developed from research done with the very chemical that gave him the disease being treated.

Source: Medindia
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