Metal Remover Clears Alzheimer's Plaques in Mice
June 21, 2001 -- A drug once accused of causing blindness and brain damage may be able to dissolve the plaques clogging the brains of people with Alzheimer's disease.
It works in mice, and early studies show that it is safe in people. It's a whole new approach to treating degenerative brain diseases -- by removing harmful metals stuck to brain cells -- and thus may open the door to new drugs for several deadly disorders.
"This is potentially a change in understanding Alzheimer's disease and other degenerative disorders where there is a metal involved," author Ashley I. Bush, MD, PhD, tells WebMD. "We think this could be a whole new class of therapeutic agent. ... We are very optimistic about the possibilities."
The concept is based on the observation that the brains of people with Alzheimer's disease have unusually high levels of copper and zinc. These metals stick to a normal brain protein, amyloid beta, and as the theory goes, are the reason why this protein forms the brain cell-killing clumps known as plaques. The metals also form so-called free radicals -- dangerous molecules that literally burn up normal cells.
"Cataracts, Lou Gehrig disease, spongiform encephalopathies [mad cow-type diseases], and Parkinson's disease -- these have in common a protein that binds a metal that we think is responsible for spawning free radicals," says Bush, director of the laboratory for oxidation biology at Harvard University.
Initial studies by Bush's team showed that chemicals that remove zinc and copper can dissolve amyloid plaques from the brains of deceased Alzheimer's patients. This led to a search for drugs that could do the same thing in living people. The search turned up a drug called clioquinol, or CQ, which was used as an antibiotic in the 1950s but was pulled off the market when it was believed to cause nerve problems. The drug was later cleared and put back on the market.
Researchers in this study used a special kind of genetically altered mouse that develops the same kind of brain plaques seen in Alzheimer's patients. After only 9 weeks of CQ treatment, half of the plaques dissolved -- and treated mice did better than untreated animals on tests of general mental function.
Metal Remover Clears Alzheimer's Plaques in Mice
June 21, 2001 -- A drug once accused of causing blindness and brain damage may be able to dissolve the plaques clogging the brains of people with Alzheimer's disease.
It works in mice, and early studies show that it is safe in people. It's a whole new approach to treating degenerative brain diseases -- by removing harmful metals stuck to brain cells -- and thus may open the door to new drugs for several deadly disorders.
"This is potentially a change in understanding Alzheimer's disease and other degenerative disorders where there is a metal involved," author Ashley I. Bush, MD, PhD, tells WebMD. "We think this could be a whole new class of therapeutic agent. ... We are very optimistic about the possibilities."
The concept is based on the observation that the brains of people with Alzheimer's disease have unusually high levels of copper and zinc. These metals stick to a normal brain protein, amyloid beta, and as the theory goes, are the reason why this protein forms the brain cell-killing clumps known as plaques. The metals also form so-called free radicals -- dangerous molecules that literally burn up normal cells.
"Cataracts, Lou Gehrig disease, spongiform encephalopathies [mad cow-type diseases], and Parkinson's disease -- these have in common a protein that binds a metal that we think is responsible for spawning free radicals," says Bush, director of the laboratory for oxidation biology at Harvard University.
Initial studies by Bush's team showed that chemicals that remove zinc and copper can dissolve amyloid plaques from the brains of deceased Alzheimer's patients. This led to a search for drugs that could do the same thing in living people. The search turned up a drug called clioquinol, or CQ, which was used as an antibiotic in the 1950s but was pulled off the market when it was believed to cause nerve problems. The drug was later cleared and put back on the market.
Researchers in this study used a special kind of genetically altered mouse that develops the same kind of brain plaques seen in Alzheimer's patients. After only 9 weeks of CQ treatment, half of the plaques dissolved -- and treated mice did better than untreated animals on tests of general mental function.
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