< strong>▎WuXi Contex Content Team Editor

About 3 billion people around the world are overweight or obese, and obesity often brings a series of health problems such as high blood lipids, diabetes, and high blood pressure question. Among the obese people, there is a type of obesity that is particularly dangerous. This is what we often call “beer belly” and “swimming ring”, which is manifested in the increase of abdominal fat. The American Heart Association’s 2021 scientific statement specifically emphasizes the effect of waist circumference on cardiovascular risk, and that excess belly fat can adversely affect health even if you’re not overweight. However, there are always some lucky ones among us with “good genes”, and “beer belly” and “swimming ring” seem to be born out of it. A paper published recently in Nature Communications, a sub-journal of “Nature”, found a key gene mutation that reduces abdominal fat. Moreover, researchers have developed weight loss therapy for this gene mutation, maybe in the future, it may only take one injection a year to give you a “gene good” effect!

Genetic factors associated with fat, analysed data from more than 360,000 people in the UK Biobank. The database contains not only the detailed genome sequence information of half a million participants, but also information on a wide variety of health conditions, allowing researchers to link genetic mutations to specific physical or disease characteristics. The researchers used body mass index (BMI)-adjusted waist/hip ratio as a measure of belly fat. The study found that this indicator has a clear causal relationship with type 2 diabetes and coronary heart disease. Analyzing the exome sequences of more than 360,000 people, the researchers found that mutations in a gene called INHBE were associated with lower waist-to-hip ratio, On average, only one in 587 people carried the mutation. It causes about 90% reduction in the level of the cytokine activin E (activin E) secreted by the liver. Individuals with this gene mutation also display lower levels of triglycerides, higher levels of high-density lipoprotein cholesterol (HDL, commonly known as “good” cholesterol), and lower levels of fasting blood sugar, which are beneficial for metabolic health.

So, can a gene mutation discovered in a lucky few lead to a weight loss therapy that benefits the wider population? Looking back at the history of new drug development, the answer is yes. It has become an emerging trend of new drug development to develop new drugs based on human genetically validated targets by studying the human genome. The lipid-lowering therapy PCSK9 inhibitor and ANGPTL3 inhibitor, which have been approved by the FDA in recent years, are both derived from genetic mutations that have been validated in a small number of human individuals. Alnylam, a star company in the RNAi field, has announced that it will target this gene and the activin E it produces to develop innovative RNAi therapies for the treatment of cardiometabolic diseases. The company’s RNAi therapy combines with the mRNA encoding the protein to degrade the mRNA in a targeted manner, thereby reducing the expression of disease-related proteins and treating the disease from the root cause. The PCSK9-targeting RNAi therapy assisted by the company in the developmentLeqvio (inclisiran) has been approved for marketing in the United States and the European Union. It only needs two injections per year to effectively reduce the incidence of low blood pressure. Density lipoprotein cholesterol (LDL-C). And the company’s latest IKARIA liver delivery platform has been further optimized for the specificity and durability of RNAi drugs. Previous studies have shown that only one injection of the drug per year is required to maintain efficacy. RNAi therapies have been approved for the market since they were first approved by the FDA in 2018. The diseases treated have also shifted from rare diseases with a small number of patients to common diseases with a large number of patients. Alnylam The company’s R&D pipeline includes treatments for common diseases such as non-alcoholic fatty liver disease, hypertension, and Alzheimer’s disease. This RNAi therapy for INHBE may be Affects more than 20% of adults worldwide.We look forward to the discovery of the INHBE gene target, the corresponding RNAi therapy It can be rapidly developed and transformed, allowing people to easily lose belly fat and improve their health with just one injection a year.

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References:

[1] Alnylam Uncovers Genetic Mutations in INHBE That Protect Against Abdominal Obesity. Retrieved July 27, 2022 from https://investors.a lnylam.com/press-release?id=26816

[2] RNAi for common diseases? Alnylam plans to forge a path forward, starting with new obesity gene target. Retrieved July 27, 2022 from https://endpts.com/rnai-for-common-diseases-alnylam-plans-to-forge-a-path-forward-starting-with-new-obesity-gene-target/

[3] Deaton, A.M. et al. (2022) Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity. Nat Commun 13, 4319 DOI: https://doi. org/10.1038/s41467-022-31757-8

[4] ABOUT ALNYLAM. Retrieved July 27, 2022 from https://www.alnylam.com/about-alnylam

[5] Nobel Prize Awarded for RNAi. Retrieved July 27, 2022 from https://www.science.org/content/article/nobel-prize-awarded-rnai

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