NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis)
NAFLD is a common liver disease with extensive fat build-up in the liver. Some patients continue to progress to more severe liver injuries, manifested by lobular inflammation, hepatocyte damage and fibrosis, as known as NASH. Abnormal liver fat accumulation by itself is associated with greater risks of cardiovascular diseases. If untreated, NASH can progress to more serious, life-threatening clinical conditions, including cirrhosis, hepatocellular carcinoma, liver transplantation, and even death.
The growing prevalence of NAFLD and NASH parallels with the dramatic rise in population of obesity and metabolic syndrome globally and in China. One study estimated that 25% of people worldwide have NAFLD, and by 2030 there will be 27 million NASH patients in China and 48 million in the U.S., respectively. Treatment for NASH is limited to lifestyle modification.
Diabetes
Diabetes is a chronic metabolic disease characterized by high blood glucose. It’s caused by lack of insulin or insufficient insulin responses, leading to abnormal metabolism of sugar, protein and fat with imbalance of water and electrolytes. If uncontrolled, diabetes could result in life threatening conditions like ketoacidosis, and chronic microvascular complications as well as increased cardiovascular risks. Diabetes is associated with genetic susceptibility, environmental factors, and lifestyle changes.
According to the International Diabetes Federation (IDF), the number of diabetes patients in the world was 463 million (prevalence 9.3%) in 2019, and is estimated to increase to 578 million (+24.8%) in 2030 and 700 million (+51.2%) in 2045. In terms of health care spending, about $760 billion was spent in 2019, which is expected to rise to $825 billion in 2030 and $845 billion in 2045. Diabetes has become one of the fastest growing health problems in the 21st century.
Obesity
Overweight and obesity are defined as abnormal or excessive fat accumulation that presents a risk to health. a body mass index (BMI, defined as body mass divided by the square of body height.) of more than 25 is considered overweight and a BMI of more than 30 is considered obese according to WHO classification. East Asian populations have lower cutoffs. Some of the known causes of obesity are diet, physical activity, lifestyles, genetic susceptibility, and endocrine disorders.
Globally, a total of 1.9 billion and 609 million adults were estimated to be overweight and obesity in 2015, respectively, representing approximately 39% of the world’s population. The prevalence of overweight and obese increased 50% and 80% over the past 40 years. Excessive body weight is strongly linked to many diseases and conditions, particularly cardiovascular diseases, type 2 diabetes mellitus, obstructive sleep apnea, certain types of cancer, osteoarthritis and asthma. As a result, obesity has been found to reduce life expectancy. Weight loss through lifestyle interventions, including dietary restriction and physical exercise are often successful in the short term, but research shows that maintaining that weight loss over the long term has proven to be rare. Medications with safe and durable efficacy are highly desired.
Dyslipidemia
Dyslipidemia, an abnormality in blood lipids consisting of high levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglyceride (TG) or low levels of high density lipoprotein cholesterol (HDL-C) singly or in combination, is an important modifiable risk factor for the development of atherosclerosis and cardiovascular disease (ASCVD). The World Health Organization estimates that dyslipidemia is associated with more than 50% of global cases of ischemic heart disease, and over 4 million deaths per year. About 80% of lipid disorders are related to diet and lifestyle, with the remainder being familial. The overall prevalence of dyslipidemia in Chinese adults is as high as 40%.
Statins are the most important drugs for these diseases. However, up to 40% of patients still have residual cardiovascular risk. In recent years, new targets for lipid-lowering therapy have become a research hotspot. With the development of new lipid-lowering drugs, the treatment of residual risk will be further improved, and eventually reduce the risk of ASCVD events.
Immune-related diseases
The immune system is the foundation of our healthy lives, to defend against external pathogens and maintain internal homeostasis.
Many diseases stem from an imbalance in the immune system:
- • Infection: invasion by harmful bacteria, viruses, and other pathogens
- • Allergy: overactivation in response to environmental antigens
- • Autoimmune diseases: overactivation in response to self-antigens
- • Cancer: failure to clear emerging and metastatic cancer cells.
There are more than 100 different autoimmune diseases and even more different cancers that affect people around the world, and many of them have no effective treatments yet. Eccogene immune programs emerge by de novo target discovery efforts based on the internal immunometabolism platform, as well as collaborative partnership.
Osteoarthritis
Osteoarthritis (OA) is a degenerative condition characterized by focal areas of loss of articular cartilage within the synovial joints. It impacts the quality of life, progressing from mild to severe as it advances from intermittent pain to chronic pain with irreversible structural damage and loss of function. It is also associated with all-cause mortality, likely due to reduced physical activity and poor self-management of other comorbidities. The prevalence of OA increases along with increasing aging and obese populations. It is estimated that 25% of males and 30% of females are affected in the 45-64 year range, and the proportion increases to 58% for men and 65% for women, respectively.
There is no cure for osteoarthritis. The majority of current treatment options, which aim to reduce symptoms and improve the quality of life, lack effectiveness in one or both aspects. More than half of patients with osteoarthritis cannot achieve sufficient analgesic effect with existing treatment options. Some comorbidities constitute contraindications to using OA therapies, such as non-steroidal anti-inflammatory drugs (NSAIDs). Thus, new therapies with superior efficacy and safety profile are highly desired.
