Can This Be the Ultimate Cure Almost One Quarter of Americans Were Waiting For?

Can This Be the Ultimate Cure Almost One Quarter of Americans Were Waiting For?

  July 01, 2020    AVisenMD

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Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder of the liver that affects hundreds of millions of people around the world, including one quarter of the total American population. It currently has no proven cure.

A first of its kind drug has been tested in a clinical trial by a group of scientists at University of California San Diego School of Medicine.It has been reported that this drug safely and effectively inhibits a key enzyme, which improves NAFLD.

This new drug, named IONIS-DGAT2 _Rx, inhibits an enzyme called Diacylglycerol- O-acyltransferase 2 (DGAT2), which is necessary for the synthesis of triglycerides. Therefore, IONIS-DGAT2 _Rx is currently under clinical investigation as a possible treatment for NAFLD and Non-alcoholic Steatohepatitis (NASH). The aim of this trial was to examine the tolerability, safety and efficacy of IONIS-DGAT2 _Rx versus placebo in reducing liver fat in patients with type 2 diabetes and NAFLD.

What is NAFLD?

NAFLD is a simple form of fatty liver where only excess fat is stored in liver tissue WITHOUT any signs of inflammation (pain and swelling of liver) or liver damage. This type of fatty liver is not linked with excessive alcohol intake.

What is NASH?

When simple NAFLD progresses toward inflammation where there is pain and swelling of the liver, then the condition is called Non-alcoholic Steatohepatitis or NASH. Only a small percentage of people with NAFLD progress to develop NASH.

There is currently no cure. Treatment primarily consists of making dietary and lifestyle changes, such as exercising regularly and losing weight, choosing a more nutritious and fat free diet and controlling other medical conditions like diabetes and hypertension (high blood pressure). Currently,  Food and Drug Administration (FDA) of USA has not approved of any drug treatment.

About the Study:

The study involved 13 weeks of treatment period of 44 participants at 16 clinical sites in Canada, Poland and Hungary. The participants were divided into a group of 29 people who received the drug and 15 people who were given a placebo. Eligible participants were aged 18–75 years, had a BMI between 27 kg/m ² - 39 kg/m ², haemoglobin A _1c (HbA _1c) levels from 7·3% to 9·5%, and liver fat content 10% or greater and agreed to maintain a stable diet and exercise routine throughout the study. The treatment group receive once weekly injection of 250 mg IONIS-DGAT2 _Rx.

Findings:

Significant reductions (roughly 30% fat reduction in majority of participants) in liver fat were noted in MRI imaging without causing an increase in blood lipid levels, blood glucose levels and liver enzyme levels like aminotransferases. Changes in body weight and gastrointestinal side-effects were also not reported when compared with the placebo.

The results from this clinical trial suggest that inhibition of DGAT2 could be a safe and efficacious strategy for treatment of NAFLD. Further investigation in patients can be explored and supported with biopsy-proven NASH. Based on this promising pharmacological target, the response to treatment observed in this specific study population could be extended to the broader population of patients worldwide with NAFLD. 

 

 

Reference: Rohit Loomba, Erin Morgan, Lynnetta Watts, Shuting Xia, Lisa A Hannan, Richard S Geary, Brenda F Baker, Sanjay Bhanot. Novel antisense inhibition of diacylglycerol O-acyltransferase 2 for treatment of non-alcoholic fatty liver disease: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. The Lancet Gastroenterology & Hepatology, 2020; DOI: 10.1016/S2468-1253(20)30186-2.