Researchers at Massachusetts General Hospital have grown "Alzheimer's in a Dish" from embryonic stem cells, a discovery that could lead to faster drug testing and a more thorough understanding of how the disease progresses, according to a new report in Nature.
Attempts to recreate Alzheimer's disease in a lab have been stymied by researchers' inability to recreate the environment of the brain. In this experiment, the researchers were able to simulate that environment by using commercially available gel.
Are you at risk of Alzheimer's? New tests aim to help find answer
Within weeks of adding genes for Alzheimer's disease to the neurons and placing the cells in the gel, researchers saw tell-tale markers of the disease. "Sure enough, we saw plaques, real plaques," lead researcher Rudolph Tanzi said. "We waited and then we saw tangles, actual tangles. It looks like you are looking at an Alzheimer's brain."
This new process will accelerate drug tests, according to Murali Doraiswamy, a neuroscience professor at Duke University.
Until now, year-long studies of mice infected with an imperfect form of the disease were the best option for determining medicines' effectiveness. But more than 20 drugs that tested well in mice failed in humans.
With the new discovery, Tanzi says, "We can test hundreds of thousands of drugs in a matter of months." He has launched a project to test 1,200 drugs already on the market and 5,000 experimental ones that passed the primary clinical testing phase.
Despite their promise, beta amyloid inhibitors fail to slow Alzheimer's
Through his experiments, Tanzi has discovered an enzyme necessary to make tangles once the plaques form. He says that drugs targeting this enzyme might provide viable treatments for Alzheimer's.
Other researches have expressed interest in using the system to study genes predisposing people to Alzheimer's, including a particularly powerful one linked to around 50% of cases.
Research supports beta-amyloid plaque theory
The Nature report appears to support the theory that beta amyloid plaques are responsible for Alzheimer's.
In the mid-1980s, George Glenner proposed that beta amyloid accumulations in the brain turn into plaques, causing neurons to make tangles, and brain cells to die. But there was no proof. Meanwhile, other models suggested tau protein caused the disease, or that the amyloid accumulation is followed by other abnormalities.
"The lack of a viable model for Alzheimer's has been the Achilles' heel of the field," says Doraiswamy. Tanzi explains, "There was a big black box of things going wrong."
According to Tanzi, his research has suggested that the plaque buildup alone may lead to tangles in the brain, thus supporting the beta amyloid plaque theory.
Doraiswamy says the next step is proving drugs that work in the petri system also successfully treat patients (Kolata, New York Times, 10/12; Preidt, HealthDay, 10/13).
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