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Salk scientists develop drug that slows Alzheimer's in mice

J147

Salk scientists developed J147, a synthetic drug shown to improve memory and prevent brain damage in mice with Alzheimer's disease.

According to the Alzheimer's Associat ion, more than 5 million Americans are living with Alzheimer's disease, the sixth leading cause of death in the country. Despite years of research, there are no disease-modifying drugs for the condition. Current FDA-approved medications, including Aricept, Razadyne and Exelon, offer only fleeting short-term benefits for patients and do nothing to slow the irreversible decline of brain function that characterizes the disease.

A drug developed by scientists in the lab of David Schubert, however, reverses memory deficits and slows Alzheimer's disease in aged mice following short-term treatment. The findings, published in Alzheimer's Research and Therapy, may pave the way to a new treatment for Alzheimer's disease in humans.

In developing the drug, known as J147, Schubert and his colleagues bucked the trend within the pharmaceutical industry, which has focused on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease. Instead, the team used living neurons grown in laboratory dishes to test whether their new synthetic compounds, which are based upon natural products derived from plants, were effective at protecting brain cells against several pathologies associated with brain aging. From the test results of each chemical iteration of the lead compound, they were able to alter their chemical structures to make them much more potent.

To test the efficacy of J147 in a much more rigorous preclinical Alzheimer's model, the team then treated mice using a therapeutic strategy that they say more accurately reflects the human symptomatic stage of Alzheimer's. Administered in the food of 20-month-old genetically engineered mice, at a stage when Alzheimer's pathology is advanced, J147 rescued severe memory loss, reduced soluble levels of amyloid, and increased neurotrophic factors essential for memory after only three months of treatment. In a different experiment, the scientists tested J147 directly against Aricept, the most widely prescribed Alzheimer's drug, and found that it performed as well or better in several memory tests.

Although J147 appears to be safe in mice, the next step will require clinical trials to determine whether the compound will prove safe and effective in humans, and Schubert and his team are currently seeking funding for such a trial.