MRNA-based therapy proves superior to the standard of care for treating hereditary tyrosinemia 1 in a mouse model.

ABSTRACT: Hereditary tyrosinemia type 1 is an inborn error of amino acid metabolism characterized by deficiency of fumarylacetoacetate hydrolase (FAH). Only limited treatment options (e.g., oral nitisinone) are available. Patients must adhere to a strict diet and face a life-long risk of complications, including liver cancer and progressive neurocognitive decline. There is a tremendous need for innovative therapies that standardize metabolite levels and promise normal development. Here, we describe an mRNA-based therapeutic approach that rescues Fah-deficient mice, a well-established tyrosinemia model. Repeated intravenous or intramuscular administration of lipid nanoparticle-formulated human FAH mRNA resulted in FAH protein synthesis in deficient mouse livers, stabilized body weight,

SUBMITTER: Cacicedo ML 

PROVIDER: S-EPMC9357842 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature