In vivo effects of the alpha-synuclein misfolding inhibitor minzasolmin supports clinical development in Parkinson’s disease.

Publication date: Jul 17, 2023

Direct targeting of alpha-synuclein (ASYN) has emerged as a disease-modifying strategy for Parkinson’s disease and other synucleinopathies which is being approached using both small molecule compounds and ASYN-targeted biologics. Minzasolmin (UCB0599) is an orally bioavailable and brain-penetrant small molecule ASYN misfolding inhibitor in clinical development as a disease-modifying therapeutic for Parkinson’s disease. Herein the results of preclinical evaluations of minzasolmin that formed the basis for subsequent clinical development are described. Pharmacokinetic evaluations of intraperitoneal 1 and 5 mg/kg minzasolmin in wildtype mice revealed parallel and dose-proportional exposures in brain and plasma. Three-month administration studies in the Line 61 transgenic mouse model of PD were conducted to measure ASYN pathology and other PD-relevant endpoints including markers of CNS inflammation, striatal DAT labeling and gait. Reductions in ASYN pathology were correlated with improved aspects of gait and balance, reductions in CNS inflammation marker abundance, and normalized striatal DAT levels. These findings provide support for human dose determinations and have informed the translational strategy for clinical trial design and biomarker selection for the ongoing clinical studies of minzasolmin in patients living with early-stage Parkinson’s disease (ClinicalTrials. gov ID: NCT04658186; EudraCT Number 2020-003265).

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Concepts Keywords
Biomarker Alpha
Nct04658186 Asyn
Parkinsons Brain
Stage Clinical


Type Source Name
disease MESH synucleinopathies
disease MESH inflammation
disease MESH gait
drug DRUGBANK Isoxaflutole
disease MESH point mutations
disease MESH dementia
disease MESH neuroinflammation
drug DRUGBANK Coenzyme M
drug DRUGBANK Tricyclazole
drug DRUGBANK Proline
disease MESH abnormalities
disease MESH posture
drug DRUGBANK Nitroglycerin
drug DRUGBANK Dopamine
disease MESH Atrophy

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