Promise of Neuroprotection in Neurodegenerative Diseases Through HGF Compounds: Kevin Church, PhD

WATCH TIME: 6 minutes

"The consistency of this mechanism across models, whether it's animal models of Alzheimer, ALS, or Parkinson, shows that it promotes HGF signaling, leading to consistent benefits in both motor and cognitive function. So, we're very confident that there is potential in this mechanism and excited to see if it translates in the clinic."

Neurotrophic factor systems, including hepatocyte growth factors (HGFs), are expressed in neurons and glia, which play key roles in maintaining neuronal survival, connectivity, metabolic stability, and regulating inflammation. Promotion of the HGF signaling to improve these effects may show promise in neurodegenerative disorders such as Alzheimer disease (AD), Parkinson disease (PD), and amyotrophic lateral sclerosis (ALS). In the past years, Athira Pharma has developed first generation (fosgonimeton) and second generation (ATH-1020 and ATH-1105) small molecules aimed to promote neurotrophic HGF system activity in these neurodegenerative disorders.

In recent studies, findings demonstrated neurotrophic, neuroprotective, and anti-inflammatory effects of positive modulators of the HGF system with fosgonimeton, ATH-1020, or ATH-1105 in preclinical models of AD, PD, and ALS, respectively.¹ In these, investigators assessed neuroprotective effects in primary neurons exposed to various insults including amyloid-β, α-synuclein protofibrils, mitochondrial toxins, excitotoxic glutamate, or proinflammatory lipopolysaccharide. Overall, the findings showed consistent treatment effects across diverse models of neurodegenerative disorders and supported the broad therapeutic potential of targeting neurotrophic HGF signaling.

Kevin Church, PhD, chief scientific officer at Athira, presented these results at the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado. At the meeting, Church sat down with NeurologyLive^® in an interview to discuss how HGF compounds target neurotrophic deficits in neurodegenerative diseases such as AD, PD, and ALS. He also spoke about the key findings regarding the impact of HGF compounds on PD and shared some of the upcoming milestones for clinical trials in AD and ALS programs.

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REFERENCES
1. Church K, Reda S, Berthiaume A, et al. Targeting Neurotrophic HGF Signaling for the Treatment of Neurodegenerative Disorders. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO.