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Phase 1 Trials of PNPLA3 siRNA in I148M Homozygous Patients with MAFLD

Elisa Fabbrini, Brian Rady, Anastasiya Koshkina, Jae Yoon Jeon, Vivaswath S. Ayyar, Cynthia Gargano, Nicholas A. DiProspero, Susan Wendel, Julia Hegge, Holly Hamilton, Zhiming Ding, Maria Afrazi, Anthony L. Nicholas, Tao Pei, Masayoshi Nakano, Shohei Ouchi, Yuki Saito, Aimi Yamashita, Ryo Tamamura, Hernan Salazar, Craig Shapiro, Tatsuya Yoshihara, Takuma Yonemura, Satoshi Inoue, Osamu Matsuoka, Mark D. Erion, Alessandro Pocai, Hideo Makimura

2024New England Journal of Medicine60 citationsDOI

Abstract

Homozygosity for the PNPLA3 risk allele is linked to liver fat accumulation. In phase 1 trials, JNJ-75220795, a hepatocyte-targeted GalNAc-conjugated PNPLA3 siRNA, reduced liver fat in PNPLA3 I148M homozygous patients with metabolic dysfunction–associated fatty liver disease.

Topics & Concepts

Fatty liverAlleleHepatocyteMedicineGeneBiologyDiseaseInternal medicineGeneticsIn vitroLiver Disease Diagnosis and TreatmentEndoplasmic Reticulum Stress and DiseaseDiabetes and associated disorders