James Parkinson (1755–1813), George Cotzias (1918–1977), Arvid Carlsson (b. 1923), Oleh Hornykiewicz (b. 1926)
Parkinson’s disease (PD) has been brought to the public’s attention thanks largely to the efforts of actor Michael J. Fox, who has spearheaded major fundraising activities seeking a cure. Heavyweight champion Muhammad Ali, the “world’s most famous Parkinson’s patient” is the visible face of this neurological disorder. First described by British physician James Parkinson in 1817, its multiple symptoms include tremors when muscles are at rest, slowness of movements, and muscle rigidity. No drug can cure PD or slow its progression, but many drugs, most notably levodopa (L-DOPA), can produce dramatic improvements.
Levodopa is inextricably linked to dopamine, a natural biochemical first synthesized in 1910 and then put aside for more than four decades. In the 1950s, Arvid Carlsson at Lund University in Sweden found dopamine in the brain—in particular, in the basal ganglia, a region responsible for smoothing out muscle movements. In 1957 he proposed that dopamine was a neurotransmitter, and in 1959 speculated that it was associated with PD. The following year, Polish-born biochemist Oleh Hornykiewicz, at the University of Vienna, provided evidence that in patients with PD, muscle-controlling brain areas were markedly deficient in dopamine. Intuitively, the treatment of PD was simple: Why not simply administer dopamine to PD patients? Unfortunately, Hornykiewicz found that dopamine failed to enter the brain from the blood.
When dopamine is synthesized in the brain, its immediate precursor is levodopa, which enters the brain after being taken by mouth. This simple explanation belies the years of effort George Cotzias devoted to perfecting a suitable levodopa schedule of doses for PD at the Brookhaven National Laboratory, leading to the first successful trials of L-DOPA, published in 1968.
Levodopa is not the final answer to PD treatment. It initially benefits 80 percent of patients, but after five years its effectiveness becomes progressively diminished, with good responses rapidly alternating with no response (on-off phenomenon). Involuntary writhing movements and body spasms (dyskinesias) are common levodopa side effects, and these were memorably depicted in Awakenings, a 1990 film based on a 1973 memoir by the British neurologist Oliver Sacks.
SEE ALSO Scopolamine (1881), Neurotransmitters (1920).
A 1965 photograph of Spanish artist Salvador Dalí, with ocelot and cane, by Roger Higgins. In the early 1980s, Dalí (1904–1989) developed Parkinson’s disease. Its debilitating effects caused him to abandon painting and contributed to his loss of joie de vivre.