Targeting Neurotrophic Factors and Preclinical Results of ALS Agent ATH-11055: Kevin Church, PhD

WATCH TIME: 5 minutes

"Neurotrophic factors are key regulators of neuron health and survival, and our small molecules aim to promote their activity in neurodegenerative conditions like ALS. Our compound, ATH-1105, has shown significant benefits in preserving motor function, neuromuscular junction integrity, and reducing neurodegeneration biomarkers in preclinical ALS studies.

ATH-1105 (Athira Pharma), an orally administered small molecule, is designed to positively modulate the neurotrophic hepatocyte growth factor (HGF) system. This system plays a key role in the maintenance and repairing of the nervous system, including stimulation of cell survival, increase in neuronal outgrowth and modulation of neuronal network repair. New preclinical data on ATH-1105 at the 2023 Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Consortium Meeting, held October 4-6, in Clearwater Beach, Florida, demonstrated its neuroprotective properties in several preclinical models of amyotrophic lateral sclerosis (ALS).¹

Data from in vitro models showed that ATH 1105 resulted in protected motor neurons from excitotoxicity, reduced TDP-43 mislocalization, preserved metabolic stability, and maintained neuromuscular junction integrity. Athira also noted that treatment with the agent improved motor and nerve function in vivo models when administered alone or in combination with riluzole. In the ALS mice models, the therapy reduced inflammation and neurodegeneration and minimized plasma neurofilament light and phosphorylated TDP-43 accumulation. Overall, investigators concluded that these findings continue to support the potential benefit of ATH-1105 as a treatment for patients with ALS.

Following the meeting, senior author Kevin Church, PhD, chief scientific officer at Athira Pharma, sat down in an interview with NeurologyLive® to discuss how neurotrophic factors play a crucial role in neuron health and survival, especially in neurodegenerative conditions like ALS. He talked about the key findings from preclinical studies on ATH-1105, and how they indicate potential benefits for patients with ALS. Additionally, Church spoke about the promising combination of ATH-1105 and riluzole in preserving motor function and slowing down the progression of ALS in preclinical models.

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REFERENCES
1. Athira Pharma Presents Preclinical Data Further Supporting the Therapeutic Potential of ATH-1105 in Amyotrophic Lateral Sclerosis (ALS). News Release. Athira Pharma. Published October 5, 2023. Accessed November 6, 2023. https://investors.athira.com/news-releases/news-release-details/athira-pharma-presents-preclinical-data-further-supporting
2. Berthiaume AA, Kleist KN, Reda SM, et al. ATH-1105, a Small-Molecule Positive Modulator of the Hepatocyte Growth Factor System, Is Neuroprotective in a Mouse Model of ALS When Administered Pre– or Post–Symptom Onset, or in Combination With Riluzole. Presented at: 2023 Annual NEALS Meeting; October 4-6; Clearwater Beach, FL. Abstract 146.