Two Potential Alzheimer's Drugs Reverse Aging in Mice

Researchers from the Salk Institute have successfully developed two possible drugs capable of blocking age-related brain damage in rats. Alzheimer's Effects On The Brain

Worldwide, 35.6 million people suffer from Alzheimer’s every year. The disease manifests itself most frequently in memory disorders and therefore other brain functions are affected. Gradually, daily activities become more and more difficult and adapting to new situations almost impossible for patients. Although scientists know that old age is the biggest risk factor for Alzheimer’s disease, they still don’t know exactly what happens at the molecular level in the brain aging process that causes the disease. In a study published last month in the eLife journal, researchers showed how two drugs could possibly block age-related brain damage in older mice by restoring some molecules to the same levels as those seen in younger mice.

In previous studies, Pamela Maher and David Schubert of the Salk Institute (California) have developed CMS121 and J147, variants of plant compounds with medicinal properties. They had shown that these drugs were able to keep neurons alive even when exposed to cellular forms of stress related to aging and Alzheimer’s disease. Since then, researchers have used them to treat anxiety in animals.

Here, they worked with a lineage of mice that can age fast. They administered CMS121 or J147 from the age of nine months, equivalent to late middle age in humans. Four months later, they tested the memory and behavior of rodents and analyzed the genetic and molecular markers in their brains.

They noted that not only the animals who received these drugs did better than other mice in memory tests, but also their brains showed differences at the cellular and molecular levels. In particular, the expression of genes associated with the energy-generating structures of the cell, the mitochondria, which have been preserved despite aging.

“This study further validated these two compounds not only as Alzheimer’s drug candidates but also as potentially more widely useful for their anti-aging effects,” says Pamela Maher. Ultimately, these two compounds can prevent the molecular changes associated with aging.

“The contribution of old age-associated detrimental processes to the disease has been largely neglected in Alzheimer’s disease drug discovery,” adds Antonio Currais, of the Salk Institute.

In other experiments, researchers observed that both drugs influenced the mitochondria by increasing levels of acetyl coenzyme A. By blocking an enzyme that normally decomposes, acetyl-CoA, or adding additional amounts of an acetyl-CoA precursor, they observed the same positive effect on mitochondria. Thus, brain cells have been protected against the molecular changes usually associated with aging.

“Some data from human studies already indicate that mitochondrial function is adversely affected by aging and is worse in the context of Alzheimer’s disease. This helps to strengthen this link,” explains Pamela Maher.

Researchers are planning future experiments to test the effects of CMS121 and J147 on the aging of other organs. Ultimately, their results can contribute to the development of new drugs for Alzheimer’s disease, they hope. “We are now using different animal models to study how this neuroprotective pathway regulates specific molecular aspects of mitochondrial biology and its effects on aging and Alzheimer’s disease,” concludes Antonio Currais.

This good news about research on Alzheimer’s disease is also revealed when the U.S. pharmaceutical company Biogen announced in early December that it managed to reduce by 23% the cognitive decline in patients treated for early Alzheimer’s disease with its drug, Aducanumab.

On October 22, the laboratory had already made headlines announcing to its investors that it would proceed in early 2020 with an application for approval with the Food and Drug Administration (FDA).