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Researchers Worm Their Way to New Alzheimer’s Treatments

Novel disease model helps identify potential therapies (Mar. 7)

According to a 2012 report from the World Health Organization, more than 35 million people worldwide currently have dementia — a number that is expected to nearly double by 2030 (66 million) and to triple by 2050 (115 million). Alzheimer’s disease (AD), the most common form of dementia, has no cure, and there are currently only a handful of approved treatments that slow, but do not prevent, the progression of symptoms.

New drug development, no matter the disease, is a slow, expensive, and risky process. Therefore, innovative techniques to study and assess the possibilities of existing drugs for different diseases can be used to alleviate the traditional burdens of cost and time. According to an article in Biological Psychiatry, researchers at the University of Washington have developed a new approach to screening potential new treatments for AD using Caenorhabditis elegans, a small transparent worm.

Their focus was on tau, a protein involved in maintaining brain-cell structure. In AD and related disorders, the tau protein becomes abnormally modified and forms clumps of proteins called aggregates. These aggregates are a hallmark of the dying nerve cells in AD and other related disorders. Diseases with abnormal tau proteins are called tauopathies.

The researchers previously developed a worm model for tauopathy by expressing human tau in C. elegans nerve cells. This model has behavioral abnormalities, accumulates abnormal tau protein, and exhibits the loss of nerve cells — all of which are general features of AD.

Using their worm model for their new study, the investigators screened a library of 1,120 drugs approved for human use and tested each drug at three different concentrations to identify compounds that suppress the effects of abnormal tau aggregation.

“We have identified six compounds capable of reliably alleviating tau-induced behavioral abnormalities in our C. elegans model for tauopathy. In a human cultured-cell model for abnormal tau protein, we have also seen that azaperone treatment can decrease the amount of abnormal tau,” said lead researcher Dr. Brian Kraemer.

Azaperone, an antipsychotic drug, normally binds to dopamine receptors in nerve cells. The researchers demonstrated that removing those receptors in either C. elegans or human cells has the same effect as treatment with azaperone, indicating that the drug and related compounds should alter abnormal tau accumulation. Other antipsychotic agents also have an effect similar to that of azaperone.

Source: Elsevier; March 7, 2013.

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