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Alzheimer’s Drug Reverses Cognitive Effects In Mice, Yale Researchers Say

August 5, 2014 by  

HARTFORD, Conn. (MCT) — Researching a new drug compound on mice, Yale School of Medicine researchers were able to reverse the effects of Alzheimer’s on learning and memory, the school announced Tuesday.

Yale School of Medicine psychiatry professor Paul Lombroso and others studied thousands of molecules, which could become drugs, in search of one or more that would inhibit the negative effects on the brain of a specific type of protein. In this latest study, scientists are showing for the first time that inhibiting the negative effects of a specific protein can reverse memory and learning deficits associated with Alzheimer’s in mice.

Yale researchers are duplicating the research to see if they get the same results with rats and non-human primates. The hope is that they will one day come up with a drug that could be used to help treat people with Alzheimer’s disease.

The protein, STriatal-Enriched protein tyrosine Phosphatase, or STEP, is present in the brain. Those with Alzheimer’s disease have elevated levels of STEP in their brains. Inhibiting the negative effects of STEP can reverse some cognitive effects of Alzheimer’s, according to the research published Tuesday in the Public Library of Science’s online journal PLoS Biology.

Having too much of the STEP protein can interfere with synapses, causing disorders in thought and behavior. The protein can keep synapses in the brain from strengthening, which is needed to convert short-term memories into long-term memories.

There is a benefit to STEP in the brain. A simple explanation is that it interferes with certain receptors in the brain that allow a person to re-learn something a different way. Too much STEP activity, however, can keep a person from learning or remembering, according to the research.

Lombroso and his collaborators looked at about 150,000 molecular compounds, narrowing them down to those that would inhibit STEP activity. The researchers examined eight of the most promising of the compounds for further study on mice.

The researchers had success with a molecular compound, or drug, they call TC-2153. The drug turned out to be a successful STEP inhibitor.

“This novel STEP inhibitor has … given a real impetus now for pharma industries to look for additional STEP inhibitors,” Lombroso said.

The doctor said he may not have the exact drug that will end up on the market, “but the whole process of drug discovery is involved screening many, many compounds and finding ones that are optimal for higher primates (people, that is).”

Christianne Kovel, of the state chapter of the Alzheimer’s Association, said: “It is an exciting and busy time in Alzheimer’s disease research with hundreds of potential therapies being tested at various stages of the research process, and many more being developed.”

More than 5 million people in the U.S. have Alzheimer’s disease, Kovel said.

–Matthew Sturdevant
The Hartford Courant

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(c)2014 The Hartford Courant (Hartford, Conn.)

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