Another way to tackle Parkinson's?

Summarized by Robert W. Griffith, MD
January 30, 2001 (Reviewed: February 18, 2003)

It's not unusual for a drug that has been used successfully to treat one disease to be shown to be effective in another. For example, the statin drugs that lower blood cholesterol are also effective in some cases of osteoporosis. We now have a new example - Australian scientists have tested a blood pressure-lowering drug, an ACE (angiotensin converting enzyme) inhibitor, in Parkinson patients, and they've found that it can help them.

Some time ago animal studies showed that the brain cells responsible for producing dopamine are closely associated with the presence of receptors, or binding-sites, for a protein called angiotensin. In the brains of patients with Parkinson's there is a reduction in the amount of angiotensin receptors very close to those cells that show degenerative changes (i.e. those in the nigrostriatum).

Because reduction of brain dopamine at these sites is known to cause symptoms of the disease, it made sense for scientists to see if an ACE inhibitor could improve the situation. Seven patients volunteered: six women and one man, aged 44 to 70, with Parkinson's lasting for 7 to 14 years. Throughout the study, they all continued on L-dopa at their regular dosage, with minor adjustments if necessary. They were given either perindopril (an ACE inhibitor known to be able to get into the brain) or a dummy medication (placebo) for 4 weeks. They then had a 4-week period with no medication (apart from the L-dopa), to allow the study medication to 'wash-out' of the body. Finally, they were given the alternative treatment (i.e. placebo or perindopril) in a crossover fashion.

At the beginning and end of each 4-week period they had a test in which they were given a standard dose of L-dopa (instead of their usual dose), and their movement disabilities were measured over the next 4 hours, using standard scales (the Webster Score and the Dyskinesia Score). The subjects also kept a 'movement' diary to register their 'on' and 'off' periods at hourly intervals through the day.

One of the subjects dropped out because of nausea and vomiting while taking perindopril. Five of the remaining 6 patients had an improvement in their movement scores using the Webster scale when taking perindopril, compared with when they were taking placebo. The improvement occurred sooner than with placebo.

L-dopa-induced improvement (the 'on' period) is normally associated with some dyskinesia, or difficulty in performing normal voluntary movements. When the subjects were taking the ACE inhibitor, this dyskinesia was not so intense. The diaries they kept showed that there was an increase in the amount of 'on' time with perindopril treatment; this was most obvious during the 3rd and 4th weeks of drug treatment.

What's the significance of these findings? That remains to be clarified, with more clinical trials that use higher doses of the drug (it had no ill-effects at the doses used in the study), given for longer periods of time (4 weeks is rather short, and benefits seemed to be continuing into the 4th week). It must be remembered that not every ACE inhibitor is likely to work, but only those that cross into the brain (e.g. perindopril, spiropril or trandolopril). In all events, the future is a little brighter for Parkinson's patients, as this study shows that new medical approaches remain possible.

Source

• The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease. KA. Reardon, SY. Chai, FAO. Mendelsohn, MK. Horne, Aust NZ J Med, 2000, vol. 30, pp. 48--53

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Parkinson's Disease & the Art of Moving

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