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Alzheimer’s Breakthrough: Drug Appeared To Reverse Symptoms In Mouse Trial

February 10, 2012

Scientists, long searching for a cure for Alzheimer´s, a reporting a dramatic breakthrough: a drug that quickly reverses the pathological, cognitive and memory deficits in mice afflicted with the disease.

The results point to the significant potential that the drug, bexarotene, could help the more than 5 million Americans suffering from the brain disease. However, they cautioned that the study was only used in mice, and that the research needs much more work to determine if the medication will show positive results in humans.

Current drugs on the market only slow the progression of Alzheimer´s disease. But the neuroscientists at Case Western Reserve University School of Medicine, hope bexarotene, or a similar variation, will someday work in humans as well.

The researchers, reporting in the US journal Science, said mice treated with the drug became rapidly smarter and the plaque in their brains that was causing Alzheimer´s started to disappear within hours.

“We were shocked and amazed,” lead author Gary Landreth, a professor in the Department of Neurosciences at Case Western Reserve University School of Medicine in Ohio, told the AFP news agency. “Things like this had never, ever been seen before.”

Landreth, explaining how bexarotene works, said levels of the protein Apolipoprotein E (ApoE) are boosted which then helps clear amyloid plaque buildup in the brain, a major trait of Alzheimer´s.

“Think of this as a garbage disposal,” said Landreth. “When we are young and healthy, all of us can basically get rid of this (amyloid) and degrade it and grind it into small bits and it gets cleared.” But many of us are “unable to do this efficiently as we age. And this is associated with mental decline or cognitive impairment,” he said.

Within six hours of receiving the drug, soluble amyloid levels in the mice fell 25 percent, ultimately reaching a 75 percent drop over time. The authors found that the mice, soon after taking the drug, began performing better in tests, showing they were able to remember things again, were more social and were able to smell again, a sense that is commonly lost in Alzheimer´s patients.

Within 72 hours after the treatments, the mice were able to associate paper with nests and began building again — another function lost in mice with Alzheimer´s.

“This is an unprecedented finding. Previously, the best existing treatment for Alzheimer’s disease in mice required several months to reduce plaque in the brain,” said study coauthor Paige Cramer, a PhD candidate at the university´s School of Medicine.

“This is a particularly exciting and rewarding study because of the new science we have discovered and the potential promise of a therapy for Alzheimer´s disease,” added Landreth. “We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans.”

If bexarotene is to work in humans, it might be best targeted at people in the early stages of the disease, because, as seen in the nest building behavior of mice with Alzheimer´s, the nests are nowhere near as good as those built by healthy mice, according to the team.

The team said clinical trials for humans are currently being designed and should produce early results in the coming year.

The US Food and Drug Administration (FDA) had previously approved bexarotene for the treatment of a rare form of cancer — cutaneous T-cell lymphoma — more than a decade ago. It was initially made by US-based Ligand Pharmaceuticals under the brand name Targretin.

Eisai Pharmaceutical from Japan bought the rights for Targretin in 2006 and it is now available through Eisai in 26 countries in Europe, North America and South America.

Scott Turner, director of the Georgetown University Medical Center’s Memory Disorders Program, who was not involved in the research, told Kerry Sheridan of AFP that he was excited by the findings. “This is a brand new way to move forward in human trials of Alzheimer’s disease and it works great with mice.”

Turner, an expert in Alzheimer´s disease, cautioned, however, that more research was needed to see if the same results can be seen in humans. “One obstacle is that the mice may not be a good model of Alzheimer´s disease. We have so many things that work in mice and we try them in humans and they just completely fail,” he said.

The FDA gives bexarotene a good safety profile, although women who are pregnant or may become pregnant are urged not to use it because of possible fetal defects. Typical side effects of the drug include diarrhea, dizziness, nausea, dry skin and trouble sleeping.

Since bexarotene is prescribed for cancer patients, there are no anecdotal reports of improved memory in humans, according to Landreth. This may be because most cancer patients do not live long enough to reach the age of when Alzheimer´s usually strikes.

Alzheimer´s and other forms of dementia affect more than 35 million people worldwide, with cases expected to double by 2030, according to Alzheimer’s Disease International which puts the annual global costs of the disease at $604 billion.

Landreth said funding and support for the research came with help from the Blanchette Hooker Rockefeller Foundation, the Thome Foundation, and the National Institutes of Health.

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Source: RedOrbit Staff & Wire Reports



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