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Study finds new and affordable treatment for Alzheimer’s disease

Study finds new and affordable treatment for Alzheimer’s disease

Researchers have discovered that a drug therapy that targets ENSA activity may be more effective than the current available treatment and also cheaper. The study has been published by the ‘Molecular Psychiatry Journal.

Alzheimer’s disease is characterized by the accumulation of amyloid B peptide (Ab). Since the 1970s, scientists have been trying to figure out how and why this happens. Takaomi and his team from RIKEN CBS created a mouse model that shows Ab accumulation and memory loss similar to what is seen with humans. They have discovered a series events in the brain that lead the formation of Ab plaques using this model mouse. The key factor is the decreased levels of the enzyme Neprilysin. This is due to a reduction in the levels of the hormone Somatostatin. Both somatostatin as well as neprilysin levels drop with age. This may explain why Alzheimer’s disease often strikes older people. The new study looked at how somatostatin regulates neprilysin levels in brains of mice with Alzheimer’s disease.

Naoto Watamura was the first author. “The first step in this process actually was the most difficult because it required us to create an in vitro method that could screen for regulators of neprilysin in conditioned medium generated from hippocampal neurons.” After this, they were able identify ENSA as the regulator. ENSA was found to reduce neprilysin activity, and that it increased to abnormally high levels when tested in mice lacking somatostatin. This means that ENSA can be controlled by somatostatin. This allows Ab to be destroyed before its accumulation.

Next, they focused on ENSA in living animal. CRISPR technology was used to create ENSA knockout mice. Then, they bred them with Alzheimer’s model mice. These mice had much lower levels of Ab than the original model mice. This indicates that abnormally high levels ENSA could be a sign or biomarker for Alzheimer’s disease. This was confirmed after the researchers found high levels of ENSA both in the brains and models of Alzheimer’s disease patients. What is ENSA doing to the brain? ENSA blocks the potassium channel in the brain’s hippocampus. This is the part of the brain that makes and recalls memories.

Watamura said that they had the same results when blocking the KATP channel, as with the ENSA knockout mouse. “We reasoned that keeping the channel open would reduce the excessive ENSA that we observed in Alzheimer’s disease.” The researchers gave the model mice diazoxide, a drug that activates KATP channel, to test their memory. They found that although the Alzheimer’s model mice showed a characteristically poor memory, those treated with diazoxide performed as well as the normal mice. A closer look at the brains revealed that the mice with Alzheimer’s disease had no Ab plaques.

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“Our findings point to a potential method of treating and preventing Alzheimer’s disease.” Watamura said that synthetic agonists for KATP channel are more affordable than Ab-targeting immunotherapy such as the FDA approved drug aducanumab.

(This story was not edited by Devdiscourse staff. It is generated automatically from a syndicated feed.

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