ABSTRACT
In the summer of 1982, California physicians were finding a baffling set of symptoms in otherwise healthy young patients: They were frozen in place, unable to move. Young individuals were arriving in hospital emergency rooms with signs of advanced Parkinson’s disease, including the full rigidity and bradykinesia that typically only occurs in older patients at advanced stages of the disease. Facing sudden, rapid onset of what is usually a slow and gradual degeneration, doctors had to uncover what was causing this mystery. Dr. Langston of the Santa Clara Valley Medical Center in San Jose, California finally was able to identify the culprit: The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which had been present in tainted batches of synthetic heroin, selectively destroyed dopamine-producing tissue in the substantia nigra, the area heavily impacted in true Parkinson’s disease, which also explained why the affected patients all appeared to be illicit drug users. The theory was further confirmed when patients showed transient responsiveness to levodopa, which was later replicated in monkeys. The selectivity of MPTP to dopaminergic cells made it a strong analogue to the natural course of the disease, and a potentially highly translatable animal model. Parallel to an alternate toxic compound, 6-hydroxydopamine (6-OHDA), which also targets noradrenergic neurons, MPTP is now used as a reliable method for studying and testing potential therapies for Parkinson’s disease in experimental settings, including the use of stem cells to restore the lost and damaged tissues.
