Anti-inflammatory drug shows benefit in Alzheimer’s in preclinical trial

Mature neuron

As emergency healthcare improves and the global population ages, more people are faced with chronic diseases, such as neurodegenerative diseases like Alzheimer’s disease (AD). Although an effective drug for Alzheimer's disease has yet to be seen, a new study has shown promise for an experimental drug in mice, and the results may extend to the human disease.

Lead researcher Dr. Mohamed Naguib and his team at the Cleveland Clinic presented their work at the 2016 Anesthesiology Annual meeting.

The drug, NTRX-07, is believed to work by decreasing the amount of inflammation caused by the plaques and tangles of protein aggregates, a hallmark progression of AD, as well as by boosting the function of neighboring neurons and regenerative cells in the brain.

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"NTRX-07 uses a different mechanism than many other Alzheimer's drugs currently available, as it targets the cause of the disease, not just the symptoms," Naguib said in a release.

The researchers fell upon the drug and its potential for AD therapy while searching for an anti-inflammatory drug used in a type of chronic pain called neuropathic pain. The inflammatory pathways clearly overlap in the disease models of neuropathic pain and neurodegenerative diseases like AD.

In mice bred to manifest AD-like symptoms, they found that inflammation affects the microglial cells, immune cells linked to the healthy removal of the classical AD protein aggregates that cause inflammation. They found that NTRX-07 targets CB2 receptors on glial cells and triggers the beneficial anti-inflammatory response of the glial cells. 

As well as preventing inflammation in these mice, it was apparent that NTRX-07 was also acting to boost the levels of a transcription factor called SOX2, a protein that regulates the expression of genes involved in the generation of new brain cells. In the brain of an AD-like mouse the levels of SOX2 are attenuated but returned to normal levels when NTRX-07 was given.