***Extracted from HCP Live***

Etienne Sibille, PhD: Innovations in Cognitive Pathology (hcplive.com)

Discoveries into the pathology of cognitive deficit may lead way toward significant innovations in the treatment of dementia, Alzheimer disease, and other relevant conditions. The breakthroughs may also help to bridge the treatment outcomes associated between psychiatric and cognitive disease.

In an interview with HCPLive during the American Psychiatric Association (APA) 2024 Annual Meeting in New York, NY, this month, Etienne Sibille, PhD, deputy director and senior scientist of the Campbell Family Mental Health Research Institute at the University of Toronto, discussed his and colleagues’ recent discoveries into the role of the inhibitory pathway in brain disorders. As he explained, the pathway’s effect correlates with cognitive symptoms in each of patients with depression, schizophrenia—as well as Alzheimer disease and other age-associated cognitive impairments.

“So, we’ve developed molecules that target this pathway, that rescue its function,” Sibille said. “And in animal models now, we’ve shown that those molecules are very potent if you want to reverse the cognitive deficits that are induced in models that replicate the pathology of humans—so model depression, model Alzheimer. We can actually not just slow down the decay, but we can reverse the cognitive deficit.”

What’s more, Sibille said, the potential molecules may help regenerate dendritic spines and improve circuiting affected by aging in patients with depression and Alzheimer disease, among other conditions—thereby possibly curbing cognitive deficit development.

In the context of what role these potential targeted therapies may play relative to currently available cognitive disease therapies, Sibille envisioned they may both improve upon and complement current options.

“It’s interesting that in the context of Alzheimer, we take it for granted that we need this disease-modifying approach—we need to restore neurons,” Sibille said. “What is less appreciated is in neuropsychiatric disorders, from depression to schizophrenia, there is a similar situation where neurons are under attack. It’s a more subtle pathological signature. But we show now that we can reverse that. It’s the same in Alzheimer.”

As such, these next agents may serve more as adjunctive therapies.

On the subject of discovering more viable therapeutic targets for cognitive diseases based on these innovations, Sibille acknowledged they are working with a cross-diagnostic pathology: many relevant disorders exacerbated by worsening cognition may be universally improved by these pathways.

“And it’s exciting, because even the FDA recognize it now as, we don’t need it necessarily to treat schizophrenia or depression, but they recognize that cognitive deficit in schizophrenia or cognitive impairment in depression is a valid separate pathology that needs to be treated by different drugs,” Sibille said. “So, they’re looking for application for specifically, ways to remediate cognitive impairment.“