The title sounds like something from the old Perry Mason TV show, but it is actually the name of a book. The book is fairly famous, at least in Parkinson circles, because it tells a bizarre story that led to major breakthroughs in PD research. J. William Langston, MD, wrote the book way back in 1995, along with science journalist Jon Palfreman.
The bizarre story in a nutshell : in 1982 in the Bay Area, Dr. Langston, a neurologist, encountered six patients totally frozen – couldn’t move, couldn’t talk. No one knew what to make of them – they had received diagnoses like catatonia or hysterical paralysis. Eventually, Dr. Langston recognized their symptoms fit advanced Parkinson’s – an incredible diagnosis since no one progresses to advanced PD overnight and PD rarely impacts people in their 20s (like these patients). However, this PD diagnosis was confirmed when Dr. Langston prescribed L-Dopa (artifical dopamine) and his patients magically “unfroze”.
What did the patients have in common? They were all heroin addicts. After some detective work by Dr. Langston and others, the heroin was analyzed and was found to be not actual heroin (derived from poppies) but a “designer drug” (a manufactured drug that gave the same high as heroin). The refining process for this particular batch had been botched, introducing a toxic contaminant called MPTP. (If you’re feeling particularly geeky, the full chemical name is 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.)
So, the bottom line discovery was that MPTP caused accelerated Parkinson’s. This meant that for the first time, PD drugs could be tested on animal models. In nature, only humans get PD. With MPTP, research animals like primates and rats could be “infected” with MPTP to display parkinsonisms. Then researchers could determine the efficacy of the drug being tested to reduce these parkinsonisms.
Lest you get squeamish about animal testing, it is far more ethical and safe to test on animals first before proceeding to human testing. And the drug I take every day (Ropinirole, aka Requip) would not have been possible without animal testing. It’s not a coincidence that MPTP’s causation of parkinsonisms was confirmed in the 1980s (after the frozen addicts event in 1982) and the PD drugs I have used were put on the market in 1997 (Mirapex and Ropinirole).
The book was copyright 1995, which is a lifetime ago in PD research. A few things sounded a bit antique. One is the book’s statement that the number of neurons (100 billion, a number that has since been questioned) is fixed at birth, and you can’t grow new ones. You can grow new neurons (the $10 buck word is neurogenesis) and that is the whole basis of research into stem cell therapy. (See earlier post.)
And speaking of stem cell therapy, another antiquity from the book is the whole Bush Administration obstruction against fetal stem cells. Langston writes about eventualy sending three of his patients to Sweden, where fetal brain tissue transplants were pioneered. These were successful in improving Dr. Langston’s patients. (One of the Swedish transplant team was Patrik Brundin, now director at Van Andel Institute, see my post. ) Mercifully, dealing with fetal tissue/cells has now (largely) become a moot point, due to the Nobel-prize winning accomplishment of Sir John B. Gurdon and Shinya Yamanaka. These scientists won the 2012 Nobel Prize in Physiology for discovering that mature, specialized cells can be reprogrammed to become “pluripotent”, that is, like stem cells: immature cells capable of developing into all tissues of the body.
And the final antiquity is the use of PET scans, at the time (early 1980s) so rare, Langdon’s patients had to be shipped off to specialists in Vancouver, BC and London. Radioactive fluoradopa was injected in the patients’ veins. The rate at which the fluoradopa was absorbed in the striatum (brain parts) provided a measure of how much dopamine was lost. PET scans are now very common; this makes me wonder why PET scans isn’t used as a diagnostic tool for PD. As I suspected, the cost is high (not prohibitive but several thousand dollars) and generally not necessary versus a clinical exam by a neurologist.
Today, Dr. Langston is Scientific Director of the Parkinson’s Institute which he founded in 1989. In 2012, he was awarded the 2012 Robert A. Pritzker Prize for Leadership in Parkinson’s Research.