Groundbreaking research on Alzheimer’s disease

This autumn saw one of the biggest breakthroughs of all time in Alzheimer’s research. At this year’s Olof Rudbeck Day on 21 October, Olof Rudbeck Award winner Lars Lannfelt, Senior Consultant and Professor Emeritus of Geriatrics at Uppsala University, will lecture on the research into the new drug candidate.

Early in his career, Lars Lannfelt started researching diseases with heredity and mechanisms of disease development. He obtained his PhD in 1990 on the disease Acute Intermittent Porphyria, which gave him a good foundation in genetics and biochemistry. Soon after, Lars found a genetic change in a large family with Alzheimer’s disease in central Sweden. It was a major scientific breakthrough that became known as the Swedish mutation.

“In a single family, we were able to get a snapshot of how the disease could develop,” says Lars. “The hereditary changes are extremely rare but have great value in explaining the disease in general.”

A few years later, a general practitioner in Umeå contacted Lars about a family in the northernmost part of Sweden with many cases of dementia. Lars and his research team found a mutation with specific characteristics that was the cause of the disease in the family. The variation was named the Arctic mutation and would become the basis for the future new medicine.

“I was very interested when we found a special form of the harmful substance amyloid beta in the plaques of this family. The special form was a soluble precursor to the insoluble, long threads, the fibrils, found in plaques. It was then, in 1999, that I had the idea of attacking the precursor to the fibrils with antibodies.”

A gratifying announcement

Twenty years later, the last clinical trial was completed showing that the antibody lecanemab slows clinical deterioration in patients with Alzheimer’s disease. The drug could be the first to target the cause of the disease – not the symptoms. The study was conducted by the pharmaceutical company Eisai in collaboration with BioArctic, which Lars founded.

“The results are clear with strong statistical significance, and all primary and secondary endpoints were met,” Lars clarifies. “This is gratifying and incredibly important for Alzheimer’s research.

“The next step is to apply to the US, Japanese and European drug agencies. An approved drug is probably ready by 2024 and slightly earlier in the US. For patients, we now have a chance to slow down the progression. To what extent remains to be seen, but we are very optimistic,” says Lars.

From mutation to possible treatment for Alzheimer’s disease

Lars’ curiosity and desire to understand the molecular mechanisms behind neurodegenerative diseases have been his driving force over the years. He will talk about this at this year’s Olof Rudbeck Day, as the recipient of the 2021 Olof Rudbeck Prize, during his lecture "From mutation to possible treatment of Alzheimer’s disease".

“I have been enormously stubborn and convinced that we have been on the right track,” says Lars. “But to get good results, it’s important to surround yourself with talented collaborators, which I’ve had over the years. My wish is that we will eventually be able to completely stop the disease process in Alzheimer’s disease – especially when we get in really early in the treatment process.

“Olof Rudbeck Day is a whole day focused on the brain and dementia, and I hope that this day will give hope to those affected and their families,” concludes Lars Lannfelt.

Cecilia Yates