Preclinical Neuroinflammation Modulation and Neuroprotection With Fosgonimeton in AD: Kevin Church, PhD

WATCH TIME: 6 minutes

"Our findings indicate that fosgonimeton can act on microglia, modulating their immune response and reducing the production of reactive oxygen species—an encouraging aspect for neurodegenerative diseases. Fosgonimeton also showcased remarkable neuroprotective effects against amyloid β-induced challenges, highlighting its potential as a therapeutic agent for Alzheimer disease."

Fosgonimeton (Athira Pharma), a small molecule, is designed to improve the activity of the neurotrophic hepatocyte growth factor signaling system. Targeting the protection and repair of neuronal networks, fosgonimeton has the potential to address a broad range of neurodegenerative diseases such as Alzheimer disease (AD). Presented at the 2023 Society for Neuroscience Annual Meeting, held November 11-15, in Washington, DC, new preclinical data showed evidence of fosgonimeton treatment protecting neurons from the toxic amyloid-β and reducing hippocampal neuron loss.¹ These findings support the potential therapeutic benefit of fosgonimeton, suggesting the treatment may reduce neuroinflammation and support adult neurogenesis.

In one presentation, findings displayed the cellular mechanisms by which fosgonimeton induced anti-inflammatory effects in BV2 microglia cells. In vitro, the active metabolite of fosgonimeton showed the expression of proinflammatory mediators, reduced mitochondrial dysfunction, and decreased oxidative stress in lipopolysaccharide-stimulated microglia. In another presentation, results showed fosgonimeton’s neurotrophic and neuroprotective activity in Aβ models of AD. In vitro, the active metabolite of fosgonimeton decreased Aβ-induced neurite degeneration, tau phosphorylation, mitochondrial stress, and neuronal death.

Following the meeting, Kevin Church, PhD, chief scientific officer at Athira Pharma, sat down in an interview with NeurologyLive® to discuss how fosgonimeton demonstrated anti-inflammatory activity, specifically in modulating microglia immune responses in AD models. He also talked about mechanisms fosgonimeton employs to protect neurons against amyloid β-induced death, and how it contributes to preserving cognitive function in models of AD. In addition, Church explained the implications of the observed increase in cell proliferation in the subgranular zone, and how it contributes to the understanding of fosgonimeton 's potential impact on neurogenesis in AD models.

REFERENCES
1. Athira Pharma Presents Preclinical Data Highlighting Fosgonimeton’s Neuroprotective Effects Against Amyloid-β-Induced Pathological Alterations and Neuroinflammation in Models of Alzheimer’s Disease. News Release. Athira Pharma. Published November 15, 2023. Accessed January 2, 2024. https://investors.athira.com/news-releases/news-release-details/athira-pharma-presents-preclinical-data-highlighting