Sunday, October 27, 2019
Bill Langstons Research into Parkinsons Disease
Bill Langstons Research into Parkinsons Disease The Case of the Frozen Addicts Is Parkinsons disease a genetic disease like Huntingtons disease, or is it caused by something in the environment? By the 1980s, scientists had concluded that the disease does not seem to be genetic with their concordance studies on identical and fraternal twins. But they had searched in vain for a credible environmental cause. Then in 1985, a bizarre drug tragedy tilted the odds in favor of an environment cause and gave scientists a powerful new weapon to fight against the disease. In the summer of 1985, Jon Palfreman, the author of the book Brain Storms, was investigating reports of some drug addicts who had mysteriously been afflicted with Parkinsons. The saga had started in July 1982 at the San Jose Country Jail, where a 42-year-old drug addict woke up and found himself to be frozen, not able to walk or talk. He was transferred to the Santa Clara Valley Medical Center and examined by Bill Langston, the 39-year-old head of neurology. Langston determined that his disease was neurological ant put him in the hospitals neurobehavior unit. For several days, George lay there, immobile. Then one day, one doctor in the unit noticed that George moved his fingers as if trying to write something. So they gave him a pencil and a notepad. After several hours, George had written five to six sentences. Through the process of questions and answers, Langston found out that George was taking heroin, and that he had a girlfriend with him before he got sick. When they tracked down this woman, they found she was also rigid, like a wax doll. Over the next few days, Langston heard about four other mysterious frozen cases in the surrounding area. Langston could think of only one factor connecting all six young people drugs. They all had a history of drug abuse. The police had found heroin in their apartments. Thinking drugs might be the answer, Langston procured some of the heroin powder from the police and sent it off for analysis. It turned out that the heroin was a designer drug synthesized from chemicals in an underground lab. Langston was struck by the similarity of their symptoms to advanced Parkinsons disease. He treated them with large doses of carbidopa-levodopa. The effect was dramatic they could move and talk. But within days, they all developed severe drug-induced motor complications. While the procedure helped, it didnt reverse their neurological damage. They grew old before their time. By 2015, all but two had passed away. Langston realized that some toxin in the heroin had passed into the addicts brains and destroyed the area of the substantia nigra which makes dopamine. Identifying this toxic might lead to the discovery of the environmental cause for Parkinsons disease. A vital clue came from a report of a similar case in the 1976. A college student named Barry Kidston was trying to make a compound called 1-methyl-4-propionoxy-piperidine, or MPPP. When injected intravenously, the chemical would give a heroin-like-high. For months, Barry successfully made MPPP and used it intravenously. One day, however, he hurried a batch, and soon after injecting it into his arm, he knew something had gone wrong. Within three days, he froze up, became immobile, and could not talk. He was referred to the NIH, where it was determined that he had produced a compound call 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, or MPTP. Armed with this information, Langston and his colleagues could prove that MPTP was the toxin in the heroin taken by the six addicts. This compound MPTP was a powerful new research tool. It could cause Parkinsons in monkeys and in humans. For the first time, Parkinsons researchers had an effective animal model of the disease. Rather than working on humans, they could study Parkinsons experimentally on monkeys, explaining disease mechanisms and testing new treatments. *** In the 1980s, many scientists were hard at work trying to figure out how the brains neuron networks work. The best known of these researchers was Mahlon DeLong based at Emory University in Atlanta. Working with healthy monkeys and monkeys with Parkinsons disease induced by the neurotoxin MPTP, DeLong found out two key nodes in the neuron network the globas pallidus and the substhalamic nucleus were much more active in parkinsonian monkeys. DeLongs hypothesis was that a loss of dopamine from the substantia nigra had caused downstream nodes in the circuit to become overexcited. The resulting output signal over-inhibits the thalamus which under-excites the motor cortex, producing the classic parkinsonian inhibition of movement. To test the hypothesis, DeLong removed the subthalamic nucleus, the presumed source of the abnormal activity, to see if that would change the moneyss Parkinsons. The effect was dramatic there was an immediate reversal of slowness, rigidity, and tremor.