#2021029 - Composition comprising an RNA therapeutic targeting FAT10 and uses of same for treating disorders characterized by abnormal lipid accumulation
Yehuda Kamari, Dan Dominissini, Michal Kandel-Kfir, Gideon Rechavi, Dror Harats, Aviv Shaish
| Categories | Therapeutics & Compositions |
| Patent Status | Pending |
Background and Need
Hyperlipidemia is a general term that encompasses diseases and disorders characterized by or associated with elevated levels of lipoproteins in the blood. Hyperlipidemias include hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and elevated lipoprotein a (Lp(a)). Hypercholesterolemia is a particular prevalent form of hyperlipidemia that could be genetic or associated with obesity and type 2 diabetes.
Abnormally high blood triglyceride levels may be an indication of conditions such as cirrhosis of the liver, underactive thyroid (hypothyroidism), poorly controlled diabetes, or pancreatitis (inflammation of the pancreas). Researchers have identified triglycerides as an independent risk factor for coronary heart disease. Hypercholesterolemia, constitutes a major risk for development of atherosclerosis and coronary heart disease (CHD).
Numerous studies have demonstrated that lowering LDL-C or Non-HDL-C levels reduces morbidity and mortality risk from atherosclerotic cardiovascular disease (ASCVD). Current cholesterol-lowering medications include statins, cholesterol absorption inhibitors, and PCSK9 inhibitors. Statins are a commonly prescribed treatment for cholesterol-lowering. However, despite the availability of such lipid-lowering therapies, many high-risk patients fail to reach their guideline target LDL-C and Non-HDL-C levels. Accordingly, patients who are not at LDL-C goal, would greatly benefit from alternative cholesterol-lowering therapies, or through use of a combination of therapeutic agents.
Invention
An RNA therapeutic that reduces/prevents expression of FAT10 as well as uses thereof in the treatment of subjects suffering from hypercholesterolemia and obesity-associated co-morbidities. It was surprisingly found by the inventors of the present invention that FAT10 inhibits age-related hepatic accumulation of triglycerides and cholesterol, suggesting a specific role of FAT10 in promoting lipogenesis in hepatocytes, thus indicating that FAT10 inhibition may be used for treatment of fatty liver.
The invention includes RNA therapeutics specifically directed to inhibit the expression of FAT10. Advantages of RNA therapeutics include: (1) their ability to act on targets that are otherwise “undruggable” for a small molecule or a protein; (2) their rapid and cost-effective development, by comparison to that of small molecules or recombinant proteins; (3) the ability to rapidly alter the sequence of the mRNA construct for personalized treatments or to adapt to an evolving pathogen.
