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Evaluation of AMX0035, a Neuroprotecting and M1-Deactivating Therapeutic, in an Immunological Model of AD (Part 1)

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In Alzheimer’s disease (AD) and other neurodegenerative diseases (ND) such as ALS, neurological inflammation and cell death form a vicious cycle that is one of the main causes of decline. Mitochondrial and endoplasmic reticulum stresses mediate these pathways, accelerating inflammation and triggering apoptosis. Therefore, we developed a combination therapeutic of repurposed compounds to simultaneously reduce endoplasmic reticulum stress and mitochondrial dysfunction to halt the cycle of inflammation and cell death. To date, we have shown that our therapeutic, AMX0035, reduced inflammation and oxidative cellular death in cellular models and reduced soluble amyloid beta in a transgenic mouse model, likely by immunological clearance. While AMX0035 is a promising candidate, a series of optimization studies is needed before it will be ready for IND-enablement. We propose evaluating AMX0035 in the G93A SOD1 mouse model of ALS, a series of in vitro dose optimization studies, healthy rats for pharmacokinetics, and a stringent rat model of innate immune response. The individual components of AMX0035 are clinically well tolerated and easily dosed in our expected dose range, which will facilitate rapid translation to and evaluation in the clinic. The proposed studies therefore will enable us to bring this promising new drug candidate to patients suffering from AD and ALS.