New therapeutic molecules are promising to reverse the memory loss associated with depression and aging

The new therapeutic molecules developed at the Center for Addiction and Mental Health (CAMH) in Toronto are promising to reverse the memory loss badociated with depression and aging.

These molecules not only improve the symptoms quickly, but remarkably, also seem to renew the underlying brain deficiencies leading to memory loss in preclinical models. These findings were presented today at the annual meeting of the American Association for the Advancement of Science (AAAS) in Washington DC.

"At the present time, there is no medication to treat cognitive symptoms such as memory loss related to depression, other mental illnesses and aging," said Dr. Etienne Sibille, deputy director of the CAMH Campbell Family Institute of Mental Health Research at CAMH and senior researcher of the study. .

In the face of numerous failures in the development of drugs for the treatment of mental illness, these results are unique and promising; these compounds are highly targeted to activate damaged brain receptors that cause memory loss. he.

It took a series of studies – the most recent published in January 2019 in Molecular Neuropsychiatry – to reach this stage. First, Dr. Sibille and his team identified specific deficiencies of brain cell receptors in the GABA neurotransmitter system. They then showed that these impairments were likely to cause symptoms of mood and memory in depression and aging.

New small molecules have been invented to bind to and activate this receptor target. The idea was that they would exert a therapeutic effect by "repairing" the deficiency, which would result in an improvement of the symptoms. The molecules are chemical modifications of benzodiazepines, a clbad of anti-anxiety and sedative drugs that also activate the GABA system, but are not very targeted.

A single dose of these new molecules has been administered in preclinical models of stress-induced memory loss. Thirty minutes later, the memory performance returned to normal levels, an experiment reproduced more than 15 times. In another experiment using preclinical aging models, memory losses were rapidly reversed and performance increased to 80% after administration, essentially reaching levels seen in the young or early stages of adulthood. This improvement lasted more than two months with daily treatment.

"Older cells have regained the appearance of young brain cells, which shows that our new molecules can alter the brain in addition to improving symptoms," says Dr. Sibille. He hopes to start testing molecules in clinical research in two years. "We have shown that our molecules enter the brain, are safe, activate target cells and reverse the cognitive deficit badociated with memory loss."

If successful, the potential applications are vast. Not only are cognitive impairments related to mental illness lacking, but brain improvements suggest that these molecules may help prevent memory loss in the early stages of Alzheimer's disease, which could delay its onset.