Nav: Home

Gastrointestinal hormone measurably improved symptoms of non-alcoholic fatty liver disease

March 08, 2018

Through a randomized, double-blind, placebo-controlled phase II clinical trial, researchers at University of California San Diego School of Medicine report that small doses of NGM282, a non-tumorigenic variant of an endocrine gastrointestinal hormone, can significantly and rapidly decrease liver fat content in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). The findings, they say, represent an important proof-of-concept for the compound as there are currently no Food and Drug Administration-approved treatments for NAFLD and NASH.

The study is published in the March 5 online issue of The Lancet.

"Patients with NAFLD and NASH have had limited treatment options for years. What the results of our phase II study show is a promising future where NGM282 may be able to provide relief to these patients," said senior author Rohit Loomba, MD, director of the UC San Diego NAFLD Research Center and director of hepatology at UC San Diego School of Medicine.

NAFLD includes a spectrum of chronic hepatic (liver) diseases, with NASH being the most aggressive type. The cause of both NAFLD and NASH remains a mystery, but certain health conditions, including obesity and type 2 diabetes, can be predisposing factors. It is estimated that tens of millions of people globally are living with NAFLD and NASH. Weight loss and a healthier diet are the current standards of care.

The study involved 166 patients, ages 18 to 75, at 18 different hospitals, gastroenterology or liver clinics in the United States and Australia. Participants had confirmed NAFLD or NASH biopsies and a liver fat content of at least 8 percent. Participants were randomly assigned by a web-based computer system on a 1:1:1 model to receive 3 milligrams (mg) or 6 mg of NGM282 or a placebo injection once per day. They were then monitored biweekly over a three-month period.

Loomba explained that both the 3 mg and 6 mg doses of NGM282 produced rapid and sustained change of liver fat content. "The most promising outcome of this study was the absolute change in liver fat that we were able to measure using advanced magnetic resonance imaging (MRI) methods previously developed and validated in pilot studies conducted at the UC San Diego NAFLD Research Center. Looking from baseline to week 12, we consider participants who had a liver fat reduction of at least either a 5 percent absolute reduction or greater than 30 percent relative reduction from baseline to be clinically significant."

To measure reduction in liver fat, researchers used hepatic MRIs with proton density fat fraction. This type of imaging is extremely sensitive to changes in liver composition compared with traditional assessments of tissue samples under a microscope.

NMG282 is a non-tumorigenic variant of fibroblast growth factor 19, an endocrine gastrointestinal hormone that regulates stomach acid and is responsible for glucose and lipid metabolism in the body. It is suspected that NMG282 is able to improve liver steatosis as well as inflammation and fibrosis commonly associated with NAFLD and NASH. Study participants generally tolerated NMG282 with reported side effects including pain at the injection site, diarrhea, abdominal pain and nausea. No life-threating events or patient deaths occurred during the study. The authors said additional and longer trials are needed to fully understand the efficacy and effectiveness of NGM282.

"Moving forward, we are continuing the development of this compound for the treatment of NASH related fibrosis," said Loomba. "In this, we hope to further examine the efficacy of this hormone in improving liver histology based end-points in patients with biopsy-proven NASH with fibrosis."
Co-authors include: Stephen A. Harrison, MD, University of Oxford; Mary E. Rinella, MD, Northwestern University; Manal F. Abdelmalek, MD, Duke University; James F. Trotter, MD, Texas Digestive Disease Consultants; Angelo H. Paredes, MD, Brooke Army Medical Center; Hays L. Arnold, MD, Gastroenterology Consultants of San Antonio; Marcelo Kugelmas, MD, South Denver Gastroenterology; Mustafa R. Bashir, MD, Duke University Medical Center; Mark J. Jaros, MD, Summit Analytical; Lei Ling, PhD, Stephen J. Rossi, MD, and Alex M. DePaoli, MD, NGM Biopharmaceuticals, Inc.

Disclosure: Loomba is a member of the clinical advisory committee for this trial for NGM.

University of California - San Diego

Related Hormone Articles:

How hormone therapy slows progression of atherosclerosis
As one of the most common treatments for effectively managing menopause symptoms, hormone therapy (HT) is also known to provide multiple health benefits, including slowing the progression of atherosclerosis.
What does the "love hormone" do? It's complicated
Much of what we know about the actions of neuromodulators like oxytocin comes from behavioral studies of lab animals in standard lab conditions.
Hormone systems can still be adapted in adulthood
Behavioural biologists at Münster University have now been able to demonstrate for the first time that male guinea pigs are still able to adapt their hormone systems to changes in their social environment in adulthood.
A hormone -- plant style
Researchers from the Faculties of Chemistry and Biology at Bielefeld University have now found a method that might make the production of a biologically significant precursor of jasmonic acid more efficient and cheaper.
uOttawa researchers discover new sex hormone
When University of Ottawa biologists Kim Mitchell and Vance Trudeau began studying the effects of gene mutations in zebrafish, they uncovered new functions that regulate how males and females interact while mating.
Could pancreatitis be a stress hormone deficiency?
UT Southwestern researchers find that humans and mice with pancreatitis are deficient in a stress hormone called FGF21.
Hormone therapy associated with improved cognition
Estrogen has a significant role in overall brain health and cognitive function.
Bones secrete a stress hormone
Both rodents and humans release a bone-derived hormone called osteocalcin in response to acute stress, researchers report on Sept.
'Hunger hormone' enhances memory
A team of neuroscience researchers at the University of Southern California have identified a surprising new role for the 'hunger hormone' ghrelin.
Ribociclib plus hormone therapy extends survival for patients with premenopausal advanced hormone receptor-positive breast cancer
Adding the targeted therapy ribociclib to hormone therapy significantly improved overall survival (OS) in premenopausal patients with advanced hormone receptor-positive (HR+) breast cancer, according to results of the MONALEESA-7 Phase III clinical trial led by researchers at The University of Texas MD Anderson Cancer Center.
More Hormone News and Hormone Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at     You can read The Transition Integrity Project's report here.