New findings from exploratory analysis of Amylyx Pharmaceuticals’ PEGASUS trial provide preliminary evidence that AMX0035 engages multiple pathological pathways related to neurodegeneration, including tau, resulting in consistent changes in Alzheimer’s Disease and neurodegeneration cerebrospinal fluid (CSF) biomarkers.
The researchers suggest that AMX0035 – odium phenylbutyrate [PB] and taurursodiol [TURSO] – engages important pathways implicated in the pathogenesis of Alzheimer’s disease
The results have published in the peer-reviewed medical journal Alzheimer’s & Dementia: Translational Research & Clinical Interventions, a journal of the Alzheimer’s Association.
“Alzheimer’s disease is defined by amyloid plaques and tau tangles, but it’s now understood that these pathologies are accompanied by alterations in multiple cell and molecular pathways, including neuronal dysfunction, neurodegeneration, and oxidative stress, driving the progression of this relentless disease,” commented Steven E. Arnold, MD, Professor of Neurology at Harvard Medical School and Translational Neurology Head and Managing Director of the Interdisciplinary Brain Center and the inaugural E. Gerald Corrigan, PhD Endowed Chair at Massachusetts General Hospital.
“The results from this exploratory analysis suggest that AMX0035 engages important pathways implicated in the pathogenesis of Alzheimer’s disease and other neurodegenerative diseases.”
The exploratory analyses showed that compared to placebo, AMX0035 reduced levels of p-tau181 and total tau.
AMX0035 treatment also reduced levels of synaptic and neuronal degeneration biomarkers in the CSF, specifically neurogranin and FABP3, as well as YKL-40, a biomarker that has been shown to correlate with cortical volume loss and rate of cognitive decline.
A 2023 publication showed AMX0035 reduced YKL-40 in ALS.
“These data lend further support to the preclinical and clinical evidence that AMX0035 has the potential to treat neurodegenerative diseases associated with tau dysfunction and tau aggregation. One such disease is progressive supranuclear palsy, also known as PSP. Our ORION trial studying AMX0035 in PSP remains ongoing,” commented Camille L. Bedrosian, MD, Chief Medical Officer at Amylyx.
“There is a pressing unmet need for new and effective treatments in PSP, and we are encouraged by our findings that further support the potential of AMX0035.”