MPTP: a chemical that causes Parkinson's

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

J. William Langston, Philip Ballard, James Tetrud and Ian Irwin. Langston was director of neurology at Santa Clara Valley Medical Center, San José, California (per a Science in the Classroom note on the paper).

What happened

The 1983 report described four people (one woman, three men, aged 26 to 42) who developed marked parkinsonism after injecting an illicit "synthetic heroin" sold in northern California. Analysis of what two of them had injected found mainly MPTP (1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine) with traces of the opioid MPPP, and the authors proposed that the chemical selectively damages cells in the substantia nigra. Langston's later review counts seven original patients and reviews how the steps of MPTP's mechanism were worked out afterwards; that mechanism is not in the 1983 report.

Why it moved us toward a cure

It was the first proof that an environmental chemical can selectively kill the neurons lost in Parkinson's. It gave researchers a primate model for testing protective drugs. Langston's 2017 review lists MAO-B inhibitors aimed at neuroprotection among the translational results of MPTP research; that line ran into the DATATOP trial (see dead ends).

Outcome

Advanced. MPTP remains a standard toxin model, and Langston's review credits it with inspiring epidemiology on other toxicants such as rotenone and paraquat.

Sources

• Langston JW, Ballard P, Tetrud JW, Irwin I, "Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis", Science 1983;219:979–980 (DOI; PMID 6823561)
• Langston JW, "The MPTP Story", J Parkinsons Dis 2017;7(s1):S11-S19, DOI 10.3233/JPD-179006, PMID 28282815 (abstract)
• Science in the Classroom note on the 1983 paper (read via search summary)
• Not yet verified: the full 1983 text; the 1983 byline affiliations; the mitochondrial mechanism that the mitochondria tag on this file assumes (not read in the sources used); whether MPTP reproduces Lewy bodies (the earlier draft said it does not, which I could not source and have removed).