Dr. Lotte Knudsen began her scientific career researching laundry detergents that would prevent red dyes from ruining white clothes.
Decades later, she is the scientist behind semaglutide, the active ingredient in the hit weight-loss drugs Ozempic and Wegovy, and now hopes to harness the drug to prevent dementia.
The self-proclaimed socialist from a small town outside Copenhagen, who gave up the intellectual property rights to semaglutide and did not cash in on its massive success like Novo Nordisk executives, spearheaded the development of Ozempic, which was initially designed to treat type 2 diabetes.
The Danish scientist pioneered research on the drug’s predecessors, which culminated in groundbreaking discoveries about its ability to reduce cognitive decline in dementia patients.
Several studies she co-authored have uncovered compelling evidence that drugs similar to Ozempic can prevent hallmark symptoms, such as memory loss, before causing permanent brain damage.
Dr. Knudsen believes they can do even more.
Of the approximately seven million Americans suffering from Alzheimer’s today, it is estimated that about 81 percent have type 2 diabetes. The metabolic condition is known to increase the risk of developing the memory-robbing disease. up to 77 percent.
Dr. Lotte Knudsen pioneered research on semaglutide and its older cousins, which gave the world Ozempic and Wegovy, breakthrough drugs that have helped around five million people lose weight.
The compound he spent years researching is GLP-1, which mimics a brain hormone that regulates appetite and makes people feel full.
Dr. Knudsen helped develop liraglutide, a synthetic version of GLP-1.
Since natural GLP-1 doesn’t last long in the body, Knudsen and his team added a “spacer” to increase its ability to dissolve in the body and help it bind to a protein called albumin. This allowed him to stay in the body longer.
Building on the fundamental work done with liraglutide, Dr. Knudsen and her team focused on creating a next-generation GLP-1 analog that would offer improvements, including a longer duration of action.
This is how semaglutide, the active ingredient in Ozempic and Wegovy, was born.
Today, semaglutide has been linked to better outcomes for people with heart disease and heart failure, high blood pressure, and dementia.
Marketed as Ozempic, it is approved to treat type 2 diabetes, but is often prescribed off-label for weight loss.
Wegovy is a higher-dose version that is approved for weight loss in people who have a body mass index of at least 30, or in overweight people with a BMI of 27 or higher, who also have a medical condition caused by their weight.
The search for a cure for dementia has not gone well. Part of this is due to a general lack of understanding of what exactly causes the characteristic cognitive decline in the brain.
Most research, including that which has led to expensive and controversial treatments, has focused almost exclusively on a protein called beta-amyloid. This protein creates a sticky buildup that clogs the spaces around brain cells.
But scientists are now coming to grips with the idea that they aimed at the wrong target. A growing body of evidence postulates that twisted fibers that build up inside brain cells called tau tangles could be behind dementia.
A 2015 study published in the journal Alzheimer’s Disease Journal Co-authored with Dr. Knudsen, they investigated how mice given a semaglutide-like compound would be better able to avoid cognitive decline.
They followed the mice for four months. All of them had a predisposition to Alzheimer’s.
Mice given the drug liraglutide for four months had more neurons in a key area of the brain (the hippocampus) associated with memory, suggesting the drug could help preserve brain cells and improve memory function.
Dr. Knudsen saying last spring: “Efficacy against Alzheimer’s has not yet been proven, but it is a hypothesis we are investigating.”
Still conducting research on the applications of liraglutide, she was co-author of a study in 2016 which revealed that mice with a genetic tendency to develop tau tangles in the brain and movement problems showed better survival when given liraglutide, semaglutide’s larger cousin.
Mice treated with the drug showed a 62 percent reduction in tau tangles compared to untreated mice.
A few years later, in a study published in the journal Alzheimer’s and dementiaDr. Knudsen and his colleagues took samples from nearly 16,000 people and gave one group a drug in the same class as Ozempic, while the other group was given nothing.
After three and a half years, they found that the risk of developing dementia was 53 percent lower in the experimental group.
In studies in both humans and mice, those who received the class of medication that includes Ozempic had slower rates of cognitive decline related to fewer deposits of harmful proteins in the brain.
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In that same study, they looked at a national cohort of more than 120,000 people with diabetes. Dr. Knudsen and his scientific colleagues followed them for seven years and four months and found that people who used these drugs for a long period had a lower risk of developing dementia.
In addition to compelling evidence pointing to links between diabetes and Alzheimer’s, obesity is a known risk factor.
Research has shown a relationship between body mass index (BMI) and brain size in people around 60 years old, and has found that the higher a person’s BMI, the smaller their brain.
Research indicates that shrinking brain regions in Alzheimer’s disease they also do so in obese individuals.
Obesity can reduce resilience to Alzheimer’s-related brain damage, worsening symptoms and accelerating disease progression. It can also cause chronic inflammation, negatively affecting the brain by overstimulating immune cells and damaging nerve cells, linking it to dementia.
Meanwhile, Ozempic and Wegovy have been shown to reduce a person’s body weight by five to twenty percent. Right now, between five and seven million people are taking one of these or similar drugs from Eli Lilly, and there are early signs that obesity rates may have dropped in the United States for the first time.
A CDC report released in September found that 40 percent of American adults were obese between 2021 and 2023, up from 42 percent between 2017 and 2020.
When asked about pharmaceutical times What her goal was for the future of these drugs, Dr Knudsen said: ‘Build new innovations in cognitive impairment (dementia).
“Get GLP-1 tested appropriately in neurodegenerative diseases because a lot of science supports its potential usefulness there.”
However, semaglutide has purported disadvantages. Hundreds of Americans have joined a class-action lawsuit alleging that Novo Nordisk, the maker of Ozempic and Wegovy, failed to warn its millions of enthusiastic customers about the very real risk of serious gastrointestinal injuries, including stomach paralysis, gallbladder problems, colon removal, and more, in addition to making misleading claims about drug safety.
It’s also not clear yet, because the drugs haven’t been around long enough for researchers to have collected long-term data, whether people who stop taking one of the blockbuster drugs will quickly regain all the weight they’ve lost.
Dr. Knuden’s research focus has changed dramatically over the years. Before changing the landscape of obesity treatment, he was studying at the Technical University of Denmark.
He began working with Danish pharmaceutical company Novo on a project to discover enzymes that improve the performance of laundry detergent to prevent color bleeding and pilling of clothes.
A mishap during his research into preventing dye bleeding, which resulted in a stink bomb-like explosion in a laboratory refrigerator, coincided with Novo’s acquisition of Nordisk, a giant insulin producer.
This transition moved industrial products to a new division, Novozymes, while Knudsen’s boss became head of a small research group focused on type 2 diabetes. Dr. Knudsen then joined the fold.
She became a diabetes researcher by chance. Repeated efforts to develop compounds that activate GLP-1 receptors failed.
But Dr. Knudsen’s determination propelled the project forward, laying the foundation for later breakthroughs that became critical breakthroughs.
