Rhamnan sulfate therapy for NAFLD/NASH and circadian rhythm disorders

This invention describes compositions and methods for treatment of metabolic diseases and disorders, such as non-alcoholic fatty liver disease (NAFLD, NASH) and circadian rhythm-related disorders.

Background/problem

Rhamnan sulfate (RS) is a sulfated polysaccharide primarily composed of rhamnose, found in the green seaweed Monostroma nitidum. This complex sugar has been shown to enhance the integrity of blood vessels throughout the body, thereby improving their function. Furthermore, it has shown potential in ameliorating vascular dysfunction caused by metabolic disorders.

This extends rhamnan sulfate’s potential health benefits to diseases rooted in disrupted metabolic homeostasis and dysregulated circadian rhythms such as Non-alcoholic Steatohepatitis (NASH) and Non-alcoholic Fatty Liver Disease (NAFLD). These disorders feature a cluster of conditions that includes increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels. NAFLD is an extremely common disease that results in the buildup of fat within the liver. While it is present in approximately 25% of the population of the United States, there are no therapies to treat this disease.

There are several compounds in clinical trials for NAFLD. However, these treatments have not been very effective and have had some side effects. Some patients with NAFLD also develop its more severe form, NASH, that can result in liver damage and scarring. Despite the severity and prevalence of these conditions, there are currently no FDA-approved pharmacological therapies, leaving weight loss and liver transplantation as the only current management options.

Technology overview/solution

Researchers at UT Austin present an innovative therapeutic approach using RS to treat and or manage NAFLD, NASH and other circadian rhythm and metabolic disorders or diseases. Studies have demonstrated that RS reduces NAFLD/NASH markers in the liver when given orally as food in atherosclerosis-prone mice fed a high-fat diet. A detailed analysis of gene expression in the mice livers revealed that RS also led to a reduction in gene expression of inflammatory genes, in addition to reducing liver fat accumulation. It also significantly regulated clock genes involved in NAFLD/atherosclerosis.

To summarize, this invention provides an orally bioavailable and non-toxic composition for treating or preventing metabolic diseases or disorders, such as NAFLD, and diseases or disorders associated with circadian rhythms, such as work-shift disorder.

Benefits

First pharmacological treatment for NAFLD: Rhamnan sulfate could provide the first pharmacological treatment for NAFLD, a condition currently lacking effective therapies.
Low cost and low toxicity: Derived from green seaweed, this compound is low-cost and has very low toxicity, making it a safe and affordable treatment option.
Oral consumption: It can be taken orally on a daily basis, as a food supplement, offering a convenient mode of administration for patients.
Potential for combination therapy: Rhamnan sulfate could be combined with other treatments for NAFLD currently in clinical trials, enhancing their effectiveness.
Broad patient reach: Its affordability and safety could make it accessible to a large population of NAFLD patients, potentially transforming the treatment landscape for this condition.