TANG PRIZE/Tang Prize honors scientists for work to combat diabetes, obesity

Taipei, June 19 (CNA) Three scientists were awarded the 2024 Tang Prize in Biopharmaceutical Science for discovering the Glucagon-like peptide-1 (7-37) (GLP-1 (7-37)) stimulates insulin secretion and can be used in medication combating diabetes and obesity, the Tang Prize Selection Committee announced Wednesday in Taipei.

The three laureates -- Joel Habener, Svetlana Mojsov, and Jens Juul Holst -- were presented the award for "the discovery of GLP-1 (7-37) as having an insulinotropic factor and the development of GLP-1 (7-37)-based anti-diabetic and anti-obesity drugs," said Chang Wen-chang (張文昌), chair of the Tang Prize Selection Committee for Biopharmaceutical Science and an academician at Academia Sinica.

The laureates' discoveries laid the foundation for the further development of GLP-1 (7-37), a 31-amino acid peptide, by other scientists. The result has been the development of blockbuster drugs that have already benefited hundreds of millions of users and have great prospects, said Academia Sinica's Kung Hsing-jien (龔行健), who introduced the laureates' major contributions.

Their work surrounding GLP-1 (7-37) is also "an exemplary story of translating basic research into pharmaceutical success with major impacts on human health," Kung said, adding that at present, there are more than 500 million patients with diabetes and about 1 billion obese individuals in the world.

Type 2 diabetes, which makes up around 90 percent of the world's cases, occurs because pancreas beta cells do not secrete enough insulin, a peptide hormone that lowers blood glucose levels. The body also cannot respond to insulin properly, which causes high blood sugar and leads to severe complications.

Obesity, on the other hand, raises the risk of various diseases and is regarded as one of the most important global public health issues.

When asked about the chances of the laureates winning a Nobel Prize in the future, Kung said, "There is potential," adding that he has seen reports in various academic magazines indicating the laureates' findings are significant enough.

Chern Jenn-chuan (陳振川), CEO of the Tang Prize Foundation, noted that in the past five rounds of selections for the Tang Prize in Biopharmaceutical Science, three groups of laureates have won the Nobel Prize after receiving the Tang Prize.

The discovery

The work toward discovering GLP-1 (7-37) has an insulinotropic factor -- meaning it stimulates insulin secretion -- dates back to the early 80s. At this time, Habener, from the Massachusetts General Hospital (MGH) and an emeritus professor of medicine at Harvard Medical School published the results of cloning the preproglucagon gene from anglerfish.

Specializing in endocrinology and metabolism, Habener found that preproglucagon, a precursor protein, contains glucagon -- a peptide hormone that raises blood glucose levels -- along with another glucagon-related peptide (GRP).

Subsequent cloning of the preproglucagon gene from rats showed that it contained glucagon and two additional peptides designated GLP-1 and GLP-2, and that the GRP from anglerfish is a form of GLP-1.

Habener then collaborated with Mojsov, the head of a peptide synthesis facility at MGH who identified GLP-1 (7-37) as the active form of intestinal GLP-1. Together they showed that it is GLP-1 (7-37) that induces insulin release from the pancreas, as opposed to the entire GLP-1 (1-37) -- the whole peptide.

The discovery was critical in identifying the long-sought-after incretin -- a type of hormone released from the gut after eating, which stimulates insulin secretion from the pancreas in response to food intake -- and led to GLP-1 (7-37) being used in diabetes medication, according to an award citation released by the Tang Prize Foundation.

Mojsov made significant contributions to GLP-1 (7-37), through synthesizing -- chemically creating -- the peptide in the mid-80s. She also developed several important experimental approaches to detect the GLPs in the intestine.

She later collaborated again with Haberner and further demonstrated through human subject research that GLP-1 (7-37) stimulates insulin production, paving the way for its use in clinical settings.

Independently, Holst at the University of Copenhagen also isolated and identified GLP-1 (1-37), and subsequently the GLP-1 (7-36) amide -- another truncated form of GLP-1 that is equally potent as GLP-1 (7-37) -- as an active incretin in the mid to late 80s.

He was also lauded by the foundation for characterizing the biology and physiology of GLP-1 (7-37), demonstrating its therapeutic potential, and contributing to the development of anti-diabetic drugs.

Drugs against diabetes and obesity

The findings of Habener, Mojsov, and Holst collectively led to an era of GLP-based drugs being used to treat diabetes from 2005 and obesity from 2014. More people have started using these medications in recent years.

During clinical trials, it was observed that patients receiving GLP-based drugs experienced weight loss. Further studies revealed that GLP-1 receptors in the human brain could suppress appetite and treat obesity.

Holst also reported that GLP-1 (7-37) reduces stomach acid and slows gastric emptying, the foundation said.

After years of pharmaceutical development, there are currently at least 13 GLP-1 receptor agonist drugs -- medications that mimic the actions of incretin and activate the GLP-1 receptor -- approved by the United States Food and Drug Administration for treating diabetes, obesity, or both, the foundation added.

An oral drug called Dipeptidyl Peptidase 4 (DPP-4) inhibitors is also widely used in clinical practice to block the degradation of GLP-1 (7-37) by the enzyme DPP-4 in the human body.

This prolongs the half-life of GLP-1 (7-37), which increases the duration of insulin secretion, therefore lowering blood sugar levels, the foundation added.

Tang Prize in Biopharmaceutical Science

The committee selected 86-year-old Habener, an emeritus professor of medicine at Harvard Medical School, 77-year-old Mojsov, a Macedonian and American research associate professor at the Rockefeller University, and 78-year-old Holst, a Danish professor at the University of Copenhagen as the most deserving individuals to win this year's Tang Prize in Biopharmaceutical Science, the foundation said.

The Tang Prize, established by Ruentex Group Chairman Samuel Yin (尹衍樑) in 2012, is a set of biennial international awards to honor individuals who have made prominent contributions in four categories -- sustainable development, biopharmaceutical science, sinology, and the rule of law.

The laureates in each category will share a cash award of NT$40 million (US$1.23 million) and a NT$10 million research grant. A week-long program revolving around the award ceremony will be held in September.