A groundbreaking study from the Centre for Addiction and Mental Health (CAMH) reveals that an experimental drug known as GL-II-73 may hold the key to restoring memory and cognitive abilities in a mouse model of Alzheimer’s disease. This recent publication in Neurobiology of Aging showcases the drug’s effectiveness in enhancing memory deficits and repairing brain cell damage, bringing newfound hope for cognitive improvement, delaying the onset of Alzheimer’s, and possibly averting some of the neurological damage caused by the illness.
Alzheimer’s disease is recognized as the most prevalent type of dementia, affecting almost 50 million people globally, whether through Alzheimer’s or related forms of dementia. This condition progressively deteriorates neurological function, leading to memory impairment, decline in cognitive skills, and shifts in behavior, which significantly affect the lives of both patients and their relatives.
This research builds upon 12 years of dedicated investigation led by Dr. Etienne Sibille, the Scientific Director of the Neurobiology of Depression and Aging Program at CAMH, alongside Dr. Thomas Prevot, a Scientist in the same program, both of whom served as co-lead authors. “We have identified a crucial vulnerability in the brain pathways affected by Alzheimer’s and similar cognitive disorders, and this drug shows potential as an innovative treatment,” stated Dr. Sibille. “By reinstating neural functions and mitigating memory loss, GL-II-73 may provide an early intervention for Alzheimer’s, tackling the underlying issues of memory loss—something that current medications are unable to achieve.”
The study evaluated GL-II-73 in a mouse model of Alzheimer’s, testing both young and older mice to reflect the disease’s early and advanced stages. The study included two groups: standard mice and genetically modified mice predisposed to accumulate beta-amyloid, a characteristic feature of Alzheimer’s. These genetically modified mice either received a single dose of GL-II-73 prior to assessments or underwent a four-week continuous treatment, with memory performance evaluated across all groups.
The results revealed that GL-II-73 significantly enhanced memory in both young and older mice displaying Alzheimer’s symptoms. In mouse models at the early stage of the disease, a single dose of the drug successfully reversed memory deficits, enabling treated mice to perform comparably to healthy mice. Though chronic treatment yielded lesser effects in mice at later disease stages, it still demonstrated some capacity to improve memory impairments even after substantial cognitive decline.
The implications of these findings are promising for Alzheimer’s disease, given the absence of current treatments capable of completely halting or reversing cognitive decline. Unlike many existing drugs that focus on beta-amyloid accumulation, GL-II-73 specifically targets GABA receptors in the hippocampus, which is essential for restoring brain function and repairing damaged neural pathways. Preliminary studies indicate that the drug may also be effective for other mental health issues related to cognitive impairment, such as depression, epilepsy, and schizophrenia.
“GL-II-73 has shown remarkable potential to restore cognitive function in a mouse model of Alzheimer’s, particularly when administered early on in the disease,” explained Dr. Prevot. “Not only does the drug enhance memory, but it also promotes the growth and reinforcement of neural connections in the brain, crucial for supporting learning and memory functions. This advancement could mark a significant breakthrough in treating Alzheimer’s and other cognitive disorders.”
In 2019, CAMH aided Dr. Sibille and his team in founding Damona Pharmaceuticals, a spin-off aimed at commercializing this research through support from CAMH’s Industry Partnerships and Technology Transfer Office. “Damona was created to concentrate on developing therapies that can counter cognitive deficits and enhance the quality of life for patients with Alzheimer’s, depression, schizophrenia, and other cognitive disorders,” noted John Reilly, CEO of Damona Pharmaceuticals. “With initial funds from leading venture capital firms, we have established a strong management team and progressed the development of this lead compound, which has recently received clearance from the U.S. Food and Drug Administration (FDA) for human clinical trials. We anticipate enrolling participants for a Phase 1 clinical trial in the first half of 2025.”
Financial support for the study was provided by the Weston Brain Institute.
