New avenues for NASH therapy by targeting ACC

Article Gastroenterology & Hepatology

Advancing the global public health agenda for NAFLD: a consensus statement

Jeffrey Lazarus et al.

Summary: Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects a significant portion of the global adult population, but has received little attention from the global public health community. This has led to a lack of inclusion of NAFLD in national and international strategies and policies for non-communicable diseases, highlighting the need for a more comprehensive public health response to the disease.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Article Biochemistry & Molecular Biology

ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials

Roberto A. Calle et al.

Summary: The study showed that ACC1/2 inhibitors had a good therapeutic effect in the treatment of non-alcoholic fatty liver disease, significantly reducing liver fat content. Co-administration of PF-05221304 and PF-06865571 can reduce the incidence of adverse events and mitigate the effect of ACC inhibition on serum triglycerides.

NATURE MEDICINE (2021)

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Review Gastroenterology & Hepatology

Therapeutic pipeline in nonalcoholic steatohepatitis

Raj Vuppalanchi et al.

Summary: The therapeutic pipeline for NASH is expanding with insights into disease pathophysiology, offering potential solutions to resolve steatohepatitis or reverse fibrosis. However, there may be some clinical challenges in the use of these emerging therapies.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2021)

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Article Cell Biology

Multiple omics study identifies an interspecies conserved driver for nonalcoholic steatohepatitis

Xiao-Jing Zhang et al.

Summary: Lipotoxicity plays a crucial role in the pathogenesis of NASH, with ALOX12 shown to exacerbate NASH severity by targeting ACC1, suggesting a potential therapeutic target.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

A small molecule targeting ALOX12-ACC1 ameliorates nonalcoholic steatohepatitis in mice and macaques

Xiao-Jing Zhang et al.

Summary: The newly identified small molecule IMA-1 shows promising efficacy in treating NASH by interrupting the ALOX12-ACC1 interaction in both mouse and macaque models, comparable to ACC inhibitors. This provides proof of concept for small molecule-based therapies for NASH across different species.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Gastroenterology & Hepatology