Publications

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is associated with a spectrum of histologic manifestations, including simple steatosis, steatohepatitis, fibrosis, and cirrhosis • Because multiple metabolic and fibroinflammatory pathways are dysregulated in NAFLD and nonalcoholic steatohepatitis (NASH), patients may benefit from approaches that support multiple pathways related to normal health processes • Endogenous metabolic modulators (EMMs)…

INTRODUCTION: AXA1665 is a novel investigational amino acid (AA) composition specifically designed to impact AA imbalance, ammoniagenesis, and dysregulated anabolic activity associated with cirrhosis. METHODS: This 2-part study examined AXA1665 effects on safety, tolerability, and hepatic/muscle physiology in subjects with Child–Pugh A and B cirrhosis. Part 1 established plasma ammonia and AA concentration baselines with…

Skeletal muscle disuse leads to atrophy, declines in muscle function, and metabolic dysfunction that are often slow to recover. Strategies to mitigate these effects would be clinically relevant. In a double-blind randomized-controlled pilot trial, we examined the safety and tolerability as well as the atrophy mitigating effect of a novel amino acid composition (AXA2678), during…

Nonalcoholic fatty liver disease (NAFLD) pathogenesis and progression are complex, heterogeneous, and multifactorial. The human diet typically contains thousands of bioactive molecules that orchestrate a variety of metabolic and signaling processes in health and disease, comprising a natural combination approach. Although food composition varies widely, cumulative evidence suggests that specific dietary macronutrients and micronutrients can…

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and is associated with significant morbidity and mortality worldwide, with a high incidence in Western countries and non‐Western countries that have adopted a Western diet. NAFLD is commonly associated with components of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease,…

Dysregulation of metabolic, inflammation and fibrotic pathways are linked to NAFLD progression. Effective therapies may require coordinated combinatorial approach to address multifactorial pathology. One potential modality is via endogenous molecules, such as amino acids (AAs), which when optimally combined can elicit meaningful effects. AXA1125, comprised of 6 AAs (LIVRQNac), designed to target liver function, was…

Background: Dysregulated metabolism contributes to muscle wasting which results in decreased quality of life and morbidity and mortality in aging and disease. We previously published that AXA2678, a composition of Endogenous Metabolic Modulators (EMMs) anchored by amino acids (AA), promotes maintenance of muscle mass, prevents muscle fat accumulation, decreases pro-inflammatory cytokines and promotes myogenic myokines…

Background: In sickle cell disease (SCD), red blood cell (RBC) sickling propagates hemolysis, inflammation, vascular and endothelial injury with associated disruption in metabolic pathways including nitric oxide depletion, oxidative stress and an increased anabolic and energetic demand due to high RBC turnover. These metabolic functions highlight the role of amino acid biology in blood health…

Dysregulated nitrogen (N) handling due to impaired ureagenesis and amino acid (AA) metabolism results in a distinct plasma AA profile (eg ↓BCAA, ↑AAA) with hyperammonemia and muscle wasting in cirrhosis. While protein supplementation is standard‐of‐care for cirrhotic patients, it carries the risk of hyperammonemia and hepatic encephalopathy due to the underlying defective N metabolism and…

Background: Convergent dysregulation of metabolism, inflammation, and fibrosis appears to be central to NASH pathogenesis. Previously [Hepatology 68(1) Suppl, pg 67A: #106], we showed AXA1125, a unique composition of amino acids (LIVRQNac), positively impacted lipotoxicity, insulin resistance, inflammation and fibrosis markers in T2D subjects with NAFLD as evidenced by reductions in liver fat, HOMA‐IR, ALT,…

Background and Aims: Sarcopenia has emerged as an independent risk factor for important clinical outcomes in cirrhosis, including hepatic encephalopathy (HE). It is closely linked to protein-malnutrition and perturbation in amino acid metabolism. A late evening snack (LES), considered part of routine care, appears to improve quality-of-life parameters in cirrhotic patients. While protein supplementation is…