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Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria

Nature Communications, ISSN: 2041-1723, Vol: 15, Issue: 1, Page: 3804
2024
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Moderna Inc. Researchers Provide Details of New Studies and Findings in the Area of Propionic Acidemia (Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and ...)

2024 MAY 24 (NewsRx) -- By a News Reporter-Staff News Editor at Clinical Trials Daily -- New research on propionic acidemia is the subject of

Article Description

Messenger RNA (mRNA) therapeutics delivered via lipid nanoparticles hold the potential to treat metabolic diseases caused by protein deficiency, including propionic acidemia (PA), methylmalonic acidemia (MMA), and phenylketonuria (PKU). Herein we report results from multiple independent preclinical studies of mRNA-3927 (an investigational treatment for PA), mRNA-3705 (an investigational treatment for MMA), and mRNA-3210 (an investigational treatment for PKU) in murine models of each disease. All 3 mRNA therapeutics exhibited pharmacokinetic/pharmacodynamic (PK/PD) responses in their respective murine model by driving mRNA, protein, and/or protein activity responses, as well as by decreasing levels of the relevant biomarker(s) when compared to control-treated animals. These preclinical data were then used to develop translational PK/PD models, which were scaled allometrically to humans to predict starting doses for first-in-human clinical studies for each disease. The predicted first-in-human doses for mRNA-3927, mRNA-3705, and mRNA-3210 were determined to be 0.3, 0.1, and 0.4 mg/kg, respectively.

Bibliographic Details

Baek, Rena; Coughlan, Kimberly; Jiang, Lei; Liang, Min; Ci, Lei; Singh, Harkewal; Zhang, Hannah; Kaushal, Neeraj; Rajlic, Ivana Liric; Van, Linh; Dimen, Rain; Cavedon, Alexander; Yin, Ling; Rice, Lisa; Frassetto, Andrea; Guey, Lin; Finn, Patrick; Martini, Paolo G V

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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