There was a puzzling process at work with amyloid-β, where it was being separated from its precursor and forming clusters in individuals with dementia. The prevailing thought was that if we could prevent this aggregation or find a way to eliminate these clumps from the brain, we might halt the progression of the disease.
In 2006, this concept gained traction when a study was published in Nature, linking memory loss to a particular type of amyloid-β accumulation outside neurons.
Focus on the Goal
This discovery provided researchers with a potential target to pursue. As is often the case with complex and poorly understood diseases, they began investigating this in mice. However, it turns out that rodents don’t naturally develop Alzheimer’s. They can, though, if researchers insert a modified version of the human APP gene into their genetic makeup. With this initial mouse model, scientists got to work.
Back in 1999, Elan Pharmaceuticals developed a vaccine targeting a specific part of amyloid-β and successfully demonstrated that it helped mice eliminate plaques from their brains. Remarkably, it was effective both in very young mice, before plaque formation, and in older mice that already had the plaques.
The way vaccines work is by stimulating the body to produce antibodies against the targeted element. A few years later, Elan provided evidence that anti-amyloid antibodies could also clear plaques in these genetically modified mice when administered directly.
However, there’s often a disconnect between results in mice and those in humans. Elan’s vaccine was tested on patients with mild to moderate Alzheimer’s, but they had to halt the study involving 360 participants after some developed brain inflammation. Although Elan’s vaccine did not progress, other pharmaceutical and biotech firms remained committed to finding a solution.
Despite numerous trials, efforts to stop or reverse the disease repeatedly fell short, regardless of the methods employed. Attempts to target various components of the amyloid-β pathway often resulted in severe, sometimes fatal, side effects. Even so, amyloid-β remained the favored target. Eventually, in 2021, the Food and Drug Administration approved an antibody known as aducanumab, developed by Biogen.
