In a continuing series of laureate announcements, the Tang Prize Foundation today (June 19th) announced the 2024 Tang Prize in Biopharmaceutical Science recipients. The prestigious award has been jointly awarded to Joel F. Habener, Svetlana Mojsov, and Jens Juul Holst, for the discovery of GLP-1 (7-37) as an insulinotropic factor and the development of GLP-1 (7-37)-based anti-diabetic and anti-obesity drugs. Their work exemplifies the translation of groundbreaking basic research into pharmaceutical success with major impacts on human health.
Of the 8 billion people in the world today, as many as 500 million have diabetes, and nearly 1 billion are obese. In Taiwan, there are currently more than 2 million diabetics, and the number is increasing by 25,000 per year.[1] The rate of obesity and overweight in adults over the age of 19 exceeds 50%.[2] The two diseases lead to severe cardiovascular, kidney, eye, foot, and other complications, resulting in a heavy medical burden for both the individual and society. Fortunately, GLP-1-based therapeutics have recently become blockbuster drugs to treat obesity and diabetes, already benefiting hundreds of millions of users with prospects of even greater benefits in the future.
GLP-1 (7-37) (Glucagon-like peptide-1 (7-37)), consisting of 31 amino acids, is an intestine-secreted hormone, also known as incretin. When blood sugar levels rise, it stimulates the secretion of GLP-1. Once the bioactive GLP-1 (7-37) binds to its receptor on the β-cells of the pancreas, it triggers the release of insulin. At present, there are at least 13 GLP-1 RA (GLP-1 receptor agonists) drugs approved by the FDA for treating diabetes and obesity. This type of drug is structurally similar to GLP-1 but has a longer half-life and can enhance the GLP-1 signaling of insulin release. In addition, an emerging oral drug called DPP-4 inhibitors is also widely used in clinics. It blocks the degradation of GLP-1 (7-37) by DPP-4 in the body, thereby prolonging the function of GLP-1 (7-37) in promoting insulin secretion and lowering blood sugar. These two types of drugs regulate blood sugar physiologically and can effectively minimize side effects compared to conventional insulin injection therapy.
The journey of the exciting discovery began with cloning the anglerfish preproglucagon gene in the early 80s by Dr. Joel Habener from Mass General Hospital/ Harvard Medical School. He discovered this precursor protein contains glucagon and another glucagon-related peptide (GRP). Subsequent cloning of the rat preproglucagon gene showed that it contained glucagon and two additional peptides designated GLP-1 and GLP-2, and that the anglerfish GRP is a GLP-1. Dr. Svetlana Mojsov, working at the Endocrine Unit and head of the HHMI peptide synthesis facility at Mass General Hospital, later identified the active form of intestinal GLP-1 to be GLP-1 (7-37). She collaborated with Dr. Habener to show that GLP-1 (7-37) can induce insulin release from the pancreas rather than the entire GLP-1 (1-37). This is an important discovery that identified the long-sought-after incretin and led to its application as an anti-diabetic strategy. The efforts of Dr. Mojsov in the synthesis of GLP-1 (7-37) and the development of several experimental approaches to detect the GLPs in the intestines were critical. Dr. Habener, Dr. Mojsov, and their collaborators showed in healthy and type 2 diabetic human subjects that GLP-1 (7-37) is insulinotropic, paving the way for clinical application. Independently at the University of Copenhagen, Denmark, Dr. Jens Juul Holst also isolated and identified GLP-1 (1-37), and subsequently GLP-1 (7-36) amide as an active incretin. His lab characterized the biology and physiology of GLP-1 (7-37), demonstrated its therapeutic potential, and has been actively involved in developing anti-diabetic drugs. Dr. Holst also reported that GLP-1 (7-37) inhibits gastric acid release and slows down gastric emptying, with anti-obesity potential. During clinical trials, it was found that diabetic patients receiving this type of drug had weight loss tendencies, further promoting its application in the treatment of obesity.
Research on GLP-1 continues to reveal its far-reaching potential for physiological regulation. Beyond the aforementioned effects on the pancreas and stomach, GLP-1 has shown promising effects on other organs, including appetite suppression through the hypothalamus and benefits for the heart, liver, and kidneys. The findings of these three scientists together ushered in an era of GLP-based drugs for treating diabetes and obesity, with contributions by many from academia and industry.
About the Tang Prize
Since the advent of globalization, mankind has been able to enjoy the convenience brought forth by the advancement of human civilization and science. Yet a multitude of challenges, such as climate change, the emergence of new infectious diseases, wealth gap, and moral degradation, have surfaced along the way. Against this backdrop, Dr. Samuel Yin established the Tang Prize in December 2012. It consists of four award categories, namely Sustainable Development, Biopharmaceutical Science, Sinology, and Rule of Law. Every other year, four independent and professional selection committees, comprising many internationally renowned experts, scholars, and Nobel winners, choose as Tang Prize laureates people who have influenced and made substantive contributions to the world, regardless of ethnicity, nationality or gender. A cash prize of NT$50 million (approx. US$1.7 million) is allocated to each category, with NT$10 million (approx. US$ 0.35 million) of it being a research grant intended to encourage professionals in every field to examine mankind’s most urgent needs in the 21st century, and become leading forces in the development of human society through their outstanding research outcomes and active civic engagement.
[1] Source: Health Promotion Administration, Ministry of Health and Welfare
[2] Source: National Nutrition and Health Status Change Survey Report (2017-2020)
