TANG PRIZE/Tang Prize laureates recall efforts on diabetes, obesity drugs

Taipei, Sept. 28 (CNA) The three winners of the 2024 Tang Prize in Biopharmaceutical Science recalled in Taipei on Saturday their discovery of a peptide hormone that promotes the secretion of insulin and how it came to be used to treat diabetes and obesity.

The three laureates -- Joel Habener, Svetlana Mojsov, and Jens Juul Holst -- received their 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," the Tang Prize Selection Committee announced in June.

Holst, a Danish professor at the University of Copenhagen, took part in the laureate lectures at National Central Library in Taipei in person, while Habener and Mojsov delivered their speeches via pre-recorded video.

Holst said he was drawn to insulin-related research in 1972 when as a young surgeon he found that patients who had been operated on for gastric ulcer disease developed reactive hypoglycemia -- a condition in which blood sugar drops to abnormally low levels after eating.

"It was clearly due to insulin secretion...so the question was, what causes this hypersecretion of insulin in these patients?" the 79-year-old researcher recalled himself thinking at the time.

Insulin is a key component in regulating blood sugar. Too much of it can lead to low blood sugar while too little leads to high sugar levels, resulting in diabetes.

Holst said he hypothesized that the effect of incretin could be a possible mechanism, because incretin is a type of hormone released from the gut after eating that stimulates insulin secretion from the pancreas in response to food intake and thus lowers blood sugar.

With that hypothesis in mind, Holst and his team looked for answers, and in the mid to late 80s, they isolated and identified GLP-1 (1-37), which contained the sequence for the active form of the incretin.

"The real structure of human GLP-1 was presented for the first time in 1989," Holst said. GLP stands for glucagon-like peptide.

After GLP-1 (7-37), a truncated active form of GLP 1 (1-37), was identified as an incretin, the hormone's ability to suppress glucagon (a peptide hormone that raises blood glucose levels), reduce gastrointestinal motility (the movement of food through the digestive system), and decrease appetite was later discovered, Holst said.

There was also data that highlighted the effectiveness of GLP-1-based drugs in treating diabetes by stimulating insulin secretion in response to high blood sugar levels.

It also showed the potential to treat obesity by slowing the passage of food through the digestive system, leading to a feeling of fullness and reducing appetite, Holst said.

At a post-lecture press conference, Holst brought up some of the setbacks he faced during his research journey, which contributed to the development of blockbuster anti-diabetic and weight-loss drugs such as Semaglutide.

"There was not a lot of support in the beginning because everybody thought this was crazy," he said, noting that it was even difficult to convince Novo Nordisk to start producing the medication because the company focused primarily on insulin production.

"'Why bother with this stupid peptide?' That's what they said," Holst recalled.

Despite questions over the drug's side effects or accusations linking it to pancreatitis, he remained steadfast in his research, approaching difficulties with a "go for it" spirit, he said.

Echoing Holst, Habener said a major challenge he faced while conducting GLP-1 research in the 1980s was that the United States government once ordered a halt to research using recombinant DNA technology due to safety and ethical considerations.

As a result, the emeritus professor of medicine at Harvard Medical School had to abandon using mice in his testing at that time and instead use anglerfish, as the restriction did not apply to cold-blooded animals.

Through animal testing, the now 87-year-old Habener managed to identify the incretin and, in a subsequent collaboration with Mojsov, further established that the bioactive form stimulating insulin secretion was GLP-1 (7-37), but not the entire GLP-1 (1-37).

In her speech, Mojsov showed a page from her notebook written while she was working at Massachusetts General Hospital in Boston in 1983, and recounted how she came up with the hypothesis that the "cleaved" GLP-1 (7-37) was the active form of the entire GLP-1 (1-37) that induced insulin release from the pancreas.

"A perfect alignment between the amino acid in GLP-1 (7-37) with those (amino acid) in glucagon," the research associate professor at the Rockefeller University said.

Mojsov, who is both American and Macedonian, said GLP-1-based drugs represent the first examples of single medicines that can be used to treat multiple human disorders, from diabetes to possibly even Parkinson's disease.

She also highlighted its additional benefits, such as its positive effects on the kidneys and protective cardiovascular effects.

"I expect in the future we will see a development of other peptide-based therapeutics which can be used as treatment for multiple human disorders," she said.

Mojsov is expected to come to Taiwan before Oct. 1, when she is scheduled to join Holst at the Masters' Forums at China Medical University in Taichung.

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 share a cash award of NT$40 million (US$1.26 million) and a NT$10 million research grant.