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Lotte Bjerre Knudsen

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Lotte Bjerre Knudsen (born 10 March 1964) is a Danish scientist and university professor. She led the development of liraglutide and oversaw the development of semaglutide,[1][2] two notable drugs approved for indications in the treatment of diabetes and obesity.[2][3]

Early life and education

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Knudsen originally studied chemical engineering at the Technical University of Denmark,[citation needed] and obtained a doctorate in scientific medicine (DMSc) from the University of Copenhagen in 2014.[2]

Career

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Knudsen began work as a scientist at the pharmaceutical company Novo Nordisk in Denmark in 1989.[2] As of December 2015, she was being referred to as Scientific Vice President for Global Research at Novo-Nordisk.[4] She served as an adjunct faculty member at Aarhus University from 2015-2020, as a professor in translational medicine.[2]

Knudsen has been employed as a Chief Scientific Advisor in Research and Early Development at Novo Nordisk.[5][6]

Contributions

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While still a student, Knudsen worked at Novo Nordisk, initially working on laundry detergent enzymes. Alongside fellow student Shamkant Patkar, she discovered an enzyme capable of removing microscopic strands of cotton that pill up on clothing from repeated wear.[7]

After this project, Knudsen joined full-time as part of a research group at Novo Nordisk that aimed to identify new treatments for diabetes, by developing small molecule drugs targeting specific metabolic pathways.[7] One project revolved around glucagon-like peptide-1 (GLP-1),[7] a hormone that stimulates the production of insulin but has a short half-life of minutes in the body.[3][third-party source needed]

GLP-1 had been previously identified by researchers such as Jens Juul Holst in Denmark, who joined Novo Nordisk as a consultant,[7][full citation needed] and Joel Habener, Daniel J. Drucker, and Svetlana Mojsov at Massachusetts General Hospital.[8][9][verification needed] Knudsen's team screened numerous chemical compounds to identify whether they could bind to the GLP-1 receptor sufficiently to stimulate insulin secretion.[10]

Eventually, they developed a new compound called liraglutide, which is an agonist for the GLP-1 receptor.[11] It is a chemical analogue of GLP-1, with a fatty acid and spacer attached. These modifications increased its ability to dissolve in water and bind to albumin, which increase its bioavailability—its lifetime in the bloodstream, and so the duration of its action in the body.[3][6] Liraglutide was approved as a treatment for diabetes under the brand name Victoza in the United States in 2010.[12]

Knudsen’s team, specifically Jesper Lau and Thomas Kruse, then worked on what became semaglutide, which had greater stability and affinity to albumin, lengthening its duration of action further to a once-weekly drug.[6][13]

Semaglutide was approved in the United States under the brand name Ozempic as a treatment for type 2 diabetes in 2017,[14][15] and under the brand name Wegovy, as a first injectable (at 2.4 mg once weekly), for chronic weight management in June 2021.[16][17][needs update]

Impact

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Martin Müller and Alexander Preker, writing for Der Spiegel in January 2024, have referred to Knudsen discovery in inventing the semaglutide weight-loss injections as "revolutionary", with the "drug Wegovy... [having] changed the world," and having made Novo Nordisk "Europe's most valuable company, [more valuable] than Daimler, Bayer, Lufthansa and BMW combined".[2]

Honors and recognition

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Knudsen received the 2023 Paul Langerhans Medal by the German Diabetes Society for her work developing liraglutide.[18][19] In October 2023, she received the STAT Biomedical Innovation award,[20] and in 2024, she received the Mani L. Bhaumik Breakthrough of the Year Award.[6] In 2024 she received the Lasker Award in clinical research.[21][22] In 2024, Knudsen received the Golden Plate Award of the American Academy of Achievement, presented by Awards Council member Robert S. Langer.[23]

Further reading

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  • Underwood, C.R.; Garibay, P.; Knudsen, L.B.; Peters, G.H.; Rudolph, R. & Reedtz-Runge, S. (January 2010). "Crystal Structure of Glucagon-like Peptide-1 in Complex with the Extracellular Domain of the Glucagon-like Peptide-1 Receptor". J. Biol. Chem. 285 (1): 723–730. doi:10.1074/jbc.M109.033829. PMC 2804221. PMID 19861722. Retrieved 13 May 2024.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  • Nielsen, Malene Løvig (18 December 2015). "Pharmaceutical Researcher is New Honorary Professor at Health". AU.dk. Retrieved 13 May 2024. Lotte Bjerre Knudsen from Novo Nordisk is a new honorary professor at Health, Aarhus University. She is the person behind the discovery of liraglutide, a new class of drugs for Novo Nordisk that are used in the treatment of type 2 diabetes and obesity.

References

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  1. ^ Molteni, Megan; Chen, Elaine (30 September 2023). "GLP-1 drugs are transforming diabetes, obesity and more. Could a Nobel be next?" STAT News. [1]. "Some of the most compelling evidence for this came when Novo Nordisk began testing a once-weekly version developed by Knudsen’s team, called semaglutide. Whereas liraglutide has been shown to cut a person’s food intake by 15%, semaglutide reduced it by up to 35%."
  2. ^ a b c d e f Müller, Martin U.; Preker, Alexander & Knudsen, Lotte Bjerre (4 January 2024). "Interview with Weight Loss Drugs Inventor Lotte Bjerre Knudsen". Der Spiegel. Retrieved 6 January 2024. Lotte Bjerre Knudsen, born in 1964, studied biotechnology and has worked for the Danish pharmaceutical company Novo Nordisk since 1989, including many years in drug discovery and development. She is interested especially in the use of the peptide hormone GLP-1 to combat obesity. She has held a doctor of medical science (DMSc) in scientific medicine from the University of Copenhagen since 2014 and served as an adjunct professor in translational medicine at Aarhus University from 2015 to 2020. Before joining Novo Nordisk, she traveled on the Trans-Siberian Railway.{{cite news}}: CS1 maint: multiple names: authors list (link).
  3. ^ a b c Knudsen, L. B. & Lau, J. (11 April 2019). "The Discovery and Development of Liraglutide and Semaglutide". Front. Endocrinol. 10: 155ff. doi:10.3389/fendo.2019.00155. ISSN 1664-2392. PMC 6474072. PMID 31031702.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Nielsen, Malene Løvig (18 December 2015). "Pharmaceutical Researcher is New Honorary Professor at Health". AU.dk. Retrieved 13 May 2024. Lotte Bjerre Knudsen from Novo Nordisk is a new honorary professor at Health, Aarhus University. She is the person behind the discovery of liraglutide, a new class of drugs for Novo Nordisk that are used in the treatment of type 2 diabetes and obesity.
  5. ^ Knudsen, Lotte Bjerre (21 April 2024). "Lotte Bjerre Knudsen: Experience" (autobiographical post). LinkedIn.com. Retrieved 21 April 2024.[third-party source needed]
  6. ^ a b c d Phelan, Meagan (4 April 2024). "Innovators Who Fought to Unlock GLP-1 Drugs for Obesity Awarded Mani L. Bhaumik Breakthrough of the Year Award." AAAS. [2]
  7. ^ a b c d Molteni, Megan (17 October 2023). "How One Scientist's Determination Made Novo Nordisk an Obesity-Drug Powerhouse". STAT. Retrieved 21 April 2024.
  8. ^ Drucker, Daniel J.; Habener, Joel F. & Holst, Jens Juul (1 December 2017). "Discovery, Characterization, and Clinical Development of the Glucagon-like Peptides". J. Clin. Invest. 127 (12): 4217–4227. doi:10.1172/JCI97233. PMC 5707151. PMID 29202475. Retrieved 21 April 2024.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. ^ Dolgin, Elie (2023). "Weight-Loss-Drug Pioneer: This Biochemist [Svetlana Mojsov] Finally Gained Recognition for her Work". Nature. 624 (13 December): 506. doi:10.1038/d41586-023-03927-1. PMID 38093064. Retrieved 21 April 2024. Svetlana Mojsov led early studies of GLP-1, the hormone behind Wegovy, Ozempic and other blockbusters.
  10. ^ Molteni, Megan; Chen, Elaine (30 September 2023). "GLP-1 drugs are transforming diabetes, obesity and more. Could a Nobel be next?" STAT News. [3]. "Knudsen spent her first year as a diabetes researcher working in a cold room with three technicians to screen hundreds of thousands of compounds to see if they could wedge into the GLP-1 receptor and other targets of interest just snugly enough to stimulate insulin secretion. To make it go faster, she updated the assays so they could test 96 candidates at a time instead of just one. But it didn’t change the fact that nothing worked."
  11. ^ Molteni, Megan; Chen, Elaine (30 September 2023). "GLP-1 drugs are transforming diabetes, obesity and more. Could a Nobel be next?" STAT News. [4]. "Following that approach would soon kick off a revolution in how doctors think of and treat obesity. Knudsen created a longer-lasting analog of GLP-1 that became liraglutide, a medication approved in 2010 and sold as Victoza that helped diabetes patients control their blood sugar and lose weight. An even more effective version would soon follow in semaglutide, the active ingredient in Ozempic and Wegovy."
  12. ^ Iepsen, E. W.; Torekov, S. S.; Holst, J. J. (2015). "Liraglutide for Type 2 diabetes and obesity: a 2015 update". Expert Review of Cardiovascular Therapy. 13 (7): 753–767. doi:10.1586/14779072.2015.1054810. PMID 26106933.
  13. ^ Lau, Jesper; Bloch, Paw; Schäffer, Lauge; Pettersson, Ingrid; Spetzler, Jane; Kofoed, Jacob; Madsen, Kjeld; Knudsen, Lotte Bjerre; McGuire, James; Steensgaard, Dorte Bjerre; Strauss, Holger Martin; Gram, Dorte X.; Knudsen, Sanne Møller; Nielsen, Flemming Seier; Thygesen, Peter; Reedtz-Runge, Steffen; Kruse, Thomas (2015). "Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide". Journal of Medicinal Chemistry. 58 (18): 7370–7380. doi:10.1021/acs.jmedchem.5b00726. PMID 26308095.
  14. ^ FDA Staff (5 December 2017). "Ozempic (semaglutide) Injection". FDA.gov. Retrieved 13 May 2024. Company: Novo Nordisk Inc. / Application No.: 209637 / Approval Date: 12/05/2017
  15. ^ Clarke, Toni (5 December 2017). "FDA approves Novo Nordisk diabetes drug Ozempic." Reuters. [5]
  16. ^ Kahn, Jeremy (4 June 2021). "FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014" (press release). FDA.gov. Retrieved 13 May 2024. Today, the U.S. Food and Drug Administration approved Wegovy (semaglutide) injection (2.4 mg once weekly) for chronic weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes, or high cholesterol), for use in addition to a reduced calorie diet and increased physical activity.[better source needed]
  17. ^ Skydsgaard, Nikolaj (4 June 2021). "U.S. FDA approves Novo Nordisk's semaglutide as obesity treatment." Reuters. [6]
  18. ^ Monecke, Angela (13 September 2023). "Paul-Langerhans-Medaille geht an die "Mutter der Moleküle"". Medical-Tribune.de (in German). Retrieved 8 January 2024. Für ihre Forschung zu Liraglutid und Semaglutid erhält Dr. Lotte Bjerre Knudsen beim Diabetes Kongress die höchste Auszeichnung der DDG. / Wohlverdient: Dr. Lotte Bjerre Knudsen nahm beim Diabetes Kongress 2023 in Berlin die Paul-Langerhans-Medaille entgegen. Die Laudatio hielten Prof. Dr. Matthias Blüher und Prof. Dr. Michael Nauck gemeinsam.
  19. ^ JournalMed.de Staff (26 May 2023). "News-Medizin: Paul-Langerhans-Medaille für die Entwicklung von Liraglutid bei Adipositas und Typ-2-Diabetes". JournalMed.de (in German). Retrieved 29 May 2023. Für ihre Arbeit zur Entwicklung des GLP-1 Rezeptoragonisten (GLP-1 RA) Liraglutid, einem Grundpfeiler der modernen Adipositas- und Typ-2-Diabetes-Therapie, erhielt die Diabetes Forscherin Lotte Bjerre Knudsen beim Kongress der Deutschen Diabetes Gesellschaft (DDG) 2023 die höchste Auszeichnung der Fachgesellschaft – die Paul-Langerhans-Medaille.
  20. ^ Chen, Elaine (18 October 2023). "Lotte Knudsen, who pushed Novo Nordisk into the Ozempic era, wins STAT Innovation award". STAT. Retrieved 21 April 2024.
  21. ^ Lasker Award 2024
  22. ^ Prashant Nair (19 September 2024). "QnAs with Svetlana Mojsov, Joel Habener, and Lotte Bjerre Knudsen: Winners of the 2024 Lasker~DeBakey Clinical Medical Research Award". Proceedings of the National Academy of Sciences of the United States of America. 121 (39). doi:10.1073/PNAS.2416868121. ISSN 0027-8424. Wikidata Q130375905.
  23. ^ "Golden Plate Awardees of the American Academy of Achievement". achievement.org. American Academy of Achievement.
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