Long-term efficacy and safety of mRNA therapy in two murine models of methylmalonic acidemia.

ABSTRACT:

Background

Isolated methylmalonic acidemia/aciduria (MMA) is an ultra-rare, serious, inherited metabolic disorder with significant morbidity and mortality. Exogenously delivered mRNA encoding human methylmalonyl-CoA mutase (hMUT), the enzyme most frequently mutated in MMA, is a potential therapy to produce functional MUT enzyme in liver.

Methods

Two 12-week repeat-dose studies were conducted to evaluate the efficacy and safety of intravenously-administered hMUT mRNA encapsulated in lipid nanoparticles in two murine models of MMA.

Findings

In MMA hypomorphic mice, hMUT mRNA treatment resulted in dose-dependent and reproducible biomarker responses after each dose. Enzymatically-active MUT protein was produced in liver in a dose-dependent manner. hMUT mRNA was well-toler

SUBMITTER: An D 

PROVIDER: S-EPMC6642332 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature