Experimental drug shows promise in restoring memory in Alzheimer's model

Experimental drug shows promise in restoring memory in Alzheimer's model

A paradigm-shifting study from the Center for Addiction and Mental Health (CAMH) shows an experimental drug, GL-II-73, has the potential to restore memory and cognitive function in a mouse model of Alzheimer's disease. Recently published inNeurobiology of agingThe study shows that the drug improves memory deficits and reverses brain cell damage, which may help improve cognitive function, delay Alzheimer's progression and prevent some of the brain damage associated with the disease.

Alzheimer's disease is the most common form of dementia, and nearly 50 million people worldwide are affected by Alzheimer's disease or related dementia. It is a progressive neurological disease that causes memory loss, cognitive decline and behavioral changes and significantly impacts the lives of patients and their families.

This paper builds on 12 years of previous research led by Dr. Etienne Sibille, scientific director of the Neurobiology of Depression and Aging Program at CAMH, and Dr. Thomas Prevot, scientist from the same program who are the co-lead authors of the co-lace study. "We have uncovered a critical vulnerability to brain pathways affected by Alzheimer's and other cognitive disorders, and this drug holds promise as a novel treatment," said Dr. Sibille. "By restoring neuronal function and reversing memory deficits, GL-II-73 represents a potential early intervention for Alzheimer's disease that addresses the root cause of memory loss, something no current medications can achieve."

The study tested the drug in a mouse model of Alzheimer's disease and used both young and older mice to represent the early and later stages of the disease. Two groups were included: normal mice and mice genetically modified to be susceptible to developing beta-amyloid buildup, a hallmark of Alzheimer's disease. Genetically engineered mice either received a single dose of GL-II-73 before being tested or were treated chronically for four weeks. The researchers then assessed memory performance in all groups.

The results showed that GL-II-73 was significantly improved in younger and older mice with Alzheimer's symptoms. In early-stage disease models, a single dose reversed drug memory deficits, allowing treated mice as well as healthy controls. Chronic treatment, although less effective, was still beneficial for mice in later stages of the disease, indicating that GL-II-73 can partially improve memory impairments even after significant cognitive decline.

The results suggest the drug could have significant impact on Alzheimer's disease, which has no current treatments that can completely slow or reverse cognitive decline. Unlike many existing drugs that target beta-amyloid buildup, GL-II-73 selectively targets GABA receptors in the hippocampus to restore brain function and repair damaged neuronal connections. Early studies also suggest the drug holds promise for other mental illnesses related to cognitive impairment, including depression, epilepsy and schizophrenia.

GL-II-73 demonstrated an incredible ability to restore cognitive function in a mouse model of Alzheimer's disease, particularly when administered early in the disease. In addition to improving memory, the drug helped grow and strengthen the neural connections in the brain that are essential for maintaining learning and memory. This could be a critical step forward in treating Alzheimer's and other cognitive disorders. “

Dr. Thomas Prevot, Scientist, Neurobiology of Depression and Aging Program at Camh

In 2019, Camh supported Dr. Sibille and his team founded Damona Pharmaceuticals, a spin-off company to commercialize this research. This process was facilitated by Camh's industry partnerships and technology transfer office. “Damona was founded to focus on developing treatments that reverse cognitive deficits and improve the lives of patients with Alzheimer's disease, depression, schizophrenia and other brain disorders,” said John Reilly, CEO of Damona Pharmaceuticals. "With seed-stage funding from top venture capital firms, we have built an exceptional management team and advanced development of this lead molecule, which recently received U.S. Food and Drug Administration (FDA) clearance for human clinical trials. We look forward to enrolling patients in a Phase 1 clinical trial in the first half of 2020." 2025.”

Funding for the study was provided by the Weston Brain Institute.

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