Research Project
8973910
? DESCRIPTION (provided by applicant): Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor function and eventually cognitive decline. GM1 depletion is validated as a therapeutic target for Parkinson's disease (PD) in clinical studies in which GM1 replacement stabilized motor function loss and may be disease modifying. However, GM1 has poor pharmacologic properties that include poor potency (100 mg, SC, bid, man) and aqueous solubility (100 mg in 2 mL), no oral bioavailability and limited blood brain barrier penetration (= % crosses the BBB) that makes continuous dosing by injection, painful, patient compliance difficult, and chronic treatment undesirable for this devastating disease. Our goal in this program is to assess GM1 analogs for their pharmacodynamic properties in a PD mouse model, validate their potential efficacy for PD using a genetic PD mouse model, and ultimately proceed to nonclinical ADMET studies and an IND.
