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Science News

Chemical Mixture of Zinc, Copper Helpful In Alzheimer’s Disease, Also Likely In Parkinson’s

A rear-view mirror image of the preceding item is a report in the Archives of Neurology. Its title: “Metal-protein attenuation with iodochlorhydroxyquin [Clioquinol] targeting Ab amyloid deposition and toxicity in Alzheimer’s disease. A pilot phase 2 clinical trial.” The journal article is dated December 2003.

The clinical study, led by researchers from the University of Melbourne in Australia, finds that treatment with an antibiotic that also removes zinc and copper from tissue might benefit patients with Alzheimer’s disease (AD). The results suggest that the medication, called clioquinol, might inhibit the accumulation of amyloid plaques in the brains of AD patients. Participants in the pilot study, all with moderate disease, who received the drug showed less cognitive decline than did AD control participants. The approach to a potential AD treatment was developed by researchers at Massachusetts General Hospital, who are co-authors of the paper.

The Melbourne team sought to determine whether clinquinol – a metal-protein attenuating compound (MPAC) might help to reduce beta-amyloid levels and slow the rate of cognitive decline in patients with AD. They surmise that the compound works by inhibiting zinc and copper ions from binding to beta-amyloid, thereby helping to dissolve the protein and preventing it from accumulating.

The researchers conducted a pilot Phase II trial of their chelation therapy in 36 patients with moderately severe AD. Eighteen patients received 125 milligrams of clinquinol twice daily for 12 weeks, then 250 milligrams twice a day for weeks 13 to 24 and 375 milligrams from weeks 25 to 36. The patients were given tests to measure cognition at the beginning of the study and again at weeks four, 12, 24 and 36.

The co-authors reported that “plasma beta-amyloid levels declined in the clinquinol group and increased in the placebo contingent. Patients taking clinquinol had better cognitive scores. The findings support a proof of concept in humans,” the co-authors write, “that a drug targeting metal/beta-amyloid interactions can have a significant effect on beta-amyloid metabolism, and through this, a beneficial modification on the progression of AD.

“The safety profile and the biochemical efficacy of clinquinol in this population are sufficiently encouraging to allow for future trials to take this investigation [clioquinol itself or a pharmacologically-improved backup] targeting beta-amyloid to the next phase. This class of MPAC,” they added, “may also be considered for related conditions, such as Parkinson’s disease.”

Source Date: Mar 15 2004