The prevalence of obesity has increased so dramatically in recent years that it is of epidemic proportions. According to the World Health Organization, every year around 2.8 million people die because of obesity, and, in 2016, it affected more than 340 million children and adolescents between the ages of 5 and 19. Changes in lifestyle, physical inactivity, and diets that are increasingly calorific are factors that have caused the prevalence of obesity to almost triple since 1975. Furthermore, obesity dramatically increases the risk of developing other diseases, such as diabetes and non-alcoholic steatohepatitis.
While studying for his doctorate degree in Pharmacology and Endocrinology at the University of Copenhagen (Denmark), the human biologist Alexander Hovard Sparre-Ulrich was a part of the team that discovered a possible weapon to use in the fight against this 21st-century problem. The young man and his team discovered a naturally occurring peptide-antagonist of the GIP receptor (glucose-dependent insulinotropic polypeptide), a hormone system whose "activity in the body is correlated with being more overweight," explains Sparre-Ulrich. For this reason, antagonizing the GIP receptor (i.e. finding a substance that causes the opposite effect) could induce weight loss and mitigate metabolic disorders related to excessive food-intake. Thanks to this discovery, the Danish researcher has become one of the winners of Innovators Under 35 Europe 2018 from MIT Technology Review.
When Sparre-Ulrich realised the potential of his discovery to create new treatments, he began to seek funding and support.In 2017, he co-founded Antag Therapeutics and has been running the company as the CEO since then. The young man explains: “We use this naturally occurring antagonist to understand how the GIP system contributes to the development of obesity and type 2 diabetes through human intervention studies. Moreover, we are conducting human studies to explore the potential of antagonizing the GIP receptor in an orphan indication”.
The word 'natural' is key in this research, as it allowed Sparre-Ulrich to validate his novel approach in human studies. The researcher confirms: “What makes our project unique is that, despite being at such an early stage, we can assess the biological consequences of antagonizing the GIPR in both healthy humans and patients". This is how he has been able to demonstrate its important effects on the metabolism.
One of the issues of working with small peptides is their short half-life. The naturally occurring antagonist has a half-life of 7.5 minutes. So Antag Therapeutics has developed a GIP receptor antagonist with a half-life of "29 hours measured in pigs, which in humans will enable once-weekly dosing and makes the treatment much more convenient for patients," says Sparre-Ulrich.
At the moment, his project is in a preclinical phase in which they are studying the validity in different metabolic diseases, and later they will "move on to clinical development". Despite its embryonic state, Sparre-Ulrich and his team’s discovery also won the University of Copenhagen Innovation Prize in 2017.
For Héctor García Martín, quantitative metabolic modeling director at Lawrence Berkeley National Laboratory and a member of the jury for Innovators Under 35 Europe 2018, it is "an excellent project with a large potential impact, that is gaining a lot of ground". Another member of the jury, Nuno Arantes-Oliveira, healthcare executive and entrepreneur at Arantes Saúde, agrees and adds that the initiative "responds to a very important need in a field where positive disruption is very welcome".
By Patricia R. Guevara
Translation: Lisa Rushforth