The Frozen Addicts

The title of this post comes from a description coined by a California neurologist who, in 1982, began investigating a bizarre disease outbreak: patients with bent and twisted bodies, faces stiffened to the point that some were drooling uncontrollably, even in the summer heat resembling bodies frozen to rigidity.

As Dr. William Langston investigated further he discovered all six of these living statues had used a new form of synthetic heroin, new to the Bay Area that July. Alarmed, Langston called a press conference to warn of bad drugs on the streets.. But he - along with state and federal researchers - hurried to discover what it was about the drug was producing these startling symptoms.

To neurologists like Langston, the symptoms were bizarrely familiar. The victims, frozen into their eerie poses, despite the summer heat, resembled patients in the last debilitating stages of Parkinson's disease, an illness which progressively destroys muscle control.

What had these drug users injected, what was the particular, peculiar chemistry that had launched them into something that looked like the end-stages of one of the most intractable of all neurological diseases? And if researchers could decipher what had happened to the frozen addicts could they also decipher what was going on with Parkinson's?

As it would turn out, yes and no.

The drug on the streets had the nickname of Super Demerol; a home-brewed experiment based on the chemistry of the well-known narcotic pain killer. One of the earliest versions was cooked up by a chemistry graduate student in Maryland, who in 1977 also became a frozen addict (and later died of a cocaine overdose). As researchers explored the connection between that case and the illnesses in California five years later, they discovered that the source of the problems was in impurity in the mix.

That impurity was a knotted bundle of carbon, hydrogen and nitrogen that researchers called MPTP ( useful short-hand for its full chemical name of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.). MPTP, as it turned out, metabolizes in the body into a targeted missile. The target is a region of the mid-brain called the substantia nigra for its dark pigment. The substantia nigra contains most of the brain cells that produce the powerful neurotransmitter dopamine, essential to everything from moving muscles to feeling pleasure.

Throughout our lives, we all naturally suffer a loss of these cells - an estimated five to eight percent every decade of our lives - without dramatic consequences. No one is yet sure why, but Parkinson's is an accelerator, dramatically speeding the losses. When about 80 percent of the dopamine-producing neurons are gone, symptoms begin to flare - tremors, freezing of motion, erasing the face of expression, and gradually getting even worse.

It's that "even worse" stage that the destructive effects of MPTP can mimic so well. And as researchers like Langston realized that, they also realized that it could be a tool. They could use it to better understand - and treat not only the frozen addicts but the disease itself. They could, in fact, develop an animal model for the disease, which they subsequently did in small South American squirrel monkeys.

And this leads me to that yes and no part of the story. Before the frozen addicts, the only real treatment for Parkinson's was a drug that stimulated the production of additional dopamine in the brain, seeking to replace some of the lost neurotransmitter. Such therapy is still used today. But the animal model has allowed researchers to investigate surgeries to repair the injured region of the brain, new techniques using electrical stimulation, and more recently stem cell replacement of damaged cells.

In other words, researchers have found new ways of managing the disease. Some of the new treatments, such as the electrical stimulation, have even been used to treat the lingering symptoms of the old frozen addicts. Count those results on the yes side. On the no side, we have not yet discovered how to cure Parkinson's - although some believe that stem cell therapies offer hope - and we don't yet know what causes Parkinson's, how to predict or prevent it.

The Case of the Frozen Addicts, as Langston called his 1996 book, also posed a question that we have yet to answer. If a street-drug impurity can trigger on form of Parkinson's, could others also have a chemical source? Recent studies have found that ingestion of the pesticide Rotenone can bring on Parkinson-like symptoms in mice. Loss of motor control, stiffening of muscles, and even loss of facial expression have been noted among the rare side effects of the high blood pressure medication, Reserpine, and the heartburn drug, Metoclopramide.

It's been been almost 30 years since the frozen addicts started turning up in California hospitals. And if we ever really understand what happened there - in all its chemical peculiarities - we may yet see that revolution in understanding Parkinson's that doctors dreamed of way back when..

(Many thanks to Sarah, a winner of the Poisoner's Handbook Giveaway, for suggesting this subject)