MRNA Treatment Rescues Niemann-Pick Disease Type C1 in Patient Fibroblasts

D Furtado; C Cortez-Jugo; YH Hung; AI Bush; F Caruso

Journal article

MRNA Treatment Rescues Niemann-Pick Disease Type C1 in Patient Fibroblasts

D Furtado, C Cortez-Jugo, YH Hung, AI Bush, F Caruso

Molecular Pharmaceutics | AMER CHEMICAL SOC | Published : 2022

DOI: 10.1021/acs.molpharmaceut.2c00463

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Abstract

Messenger RNA (mRNA) holds great potential as a disease-modifying treatment for a wide array of monogenic disorders. Niemann-Pick disease type C1 (NP-C1) is an ultrarare monogenic disease that arises due to loss-of-function mutations in the NPC1 gene, resulting in the entrapment of unesterified cholesterol in the lysosomes of affected cells and a subsequent reduction in their capacity for cholesterol esterification. This causes severe damage to various organs including the brain, liver, and spleen. In this work, we describe the use of NPC1-encoded mRNA to rescue the protein insufficiency and pathogenic phenotype caused by biallelic NPC1 mutations in cultured fibroblasts derived from an NP-C1..

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University of Melbourne Researchers

Christina Cortez-Jugo Author

Ya Hui Hung Author

Ashley Bush Author

Frank Caruso Author

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Grants

Awarded by Friedreich's Ataxia Research Alliance

Funding Acknowledgements

This research was funded by the National Health and Medical Research Council (NHMRC) (Grant GNT1149990, F.C.). Y.H.H. and A.I.B. acknowledge grant funding from the Australian NPC Disease Foundation. F.C. acknowledges the award of an NHMRC Senior Principal Research Fellowship (Grant GNT1135806). C.C.-J. acknowledges support from the Friedreich's Ataxia Research Alliance and fara Australia. D.F. acknowledges the award of a Westpac Future Leader's Scholarship from the Westpac Foundation. We acknowledge the Biological Optical Microscopy Platform (BOMP) at the University of Melbourne for access to the PerkinElmer Operetta CLS High Content Imaging System.