Alzheimer’s disease (AD), the most common form of dementia, affects over six million people in the US alone. By 2050, the number of people aged over 65 with the neurodegenerative disease is anticipated to grow to more than 12 million.
Treatment options for the condition are limited. Just this week, Biogen’s aducanumab became the first new Alzheimer’s therapy to be approved by the US in 20 years – and scientific opinion is divided over how beneficial the treatment will be for patients.
Over 100 prospective AD drugs have failed in trials over the past decade, and the few that have shown promise focus on slowing the progression of the disease, rather than tackling its underlying causes. Now, new research suggests that medicine could someday achieve what is currently impossible: reversing the effects of Alzheimer’s.
A personalised approach
A trial using precision medicine to target the key drivers of Alzheimer’s has become the first to show improvement in patients living with the disease. The results, published in medRxiv in May, showed that 21 of the 25 participants in the small, proof-of-concept study demonstrated improved cognition after treatment. The findings established that using personalised treatments to target a range of contributors to Alzheimer’s is effective enough to warrant a larger clinical trial.
Previous AD clinical trials have focused on a single treatment modality. The study’s co-lead author Dr Dale Bredesen, neurodegenerative disease expert and chief science officer at AD-focused Apollo Health, says treating Alzheimer’s with a single therapy is a “blind approach” that often fails to address the primary drivers behind an individual’s cognitive decline.
“You’re not asking ‘why did the person get cognitive decline?’,” he says. “You’re just giving them a drug.”
The subtypes of Alzheimer’s
In their pursuit of a personalised approach to Alzheimer’s, the researchers behind the study identified the primary drivers of the disease, which can range from pathogens and toxins to vascular disease.
“There hadn’t been success with precision medicine for Alzheimer’s because people hadn’t really made deep dives into what is causing this in each person,” Bredesen explains. “So in our case, we looked at many different variables, we determined the contributors to cognitive decline for each person, and then we targeted those.
“We described subtypes of Alzheimer’s based on these various parameters back in 2015, and we’ve seen this in the trial as well,” he says. “The idea is, you have to flip the script instead of just treating everybody with a Procrustean approach.”
Bredesen likens the team’s Alzheimer’s strategy to precision medicine in cancer, where the driving genetic mutations in an individual patient are identified and then targeted.
“I think that this model, understanding what Alzheimer’s actually is, is allowing us to see it in a much more accurate light than in the past,” he says, “and is allowing us to have much better results than have ever been documented previously.”
The team’s hypothesis about the nature of Alzheimer’s has long been met with scepticism, Bredesen says. The researchers first proposed a four-arm trial exploring multiple potential therapies for Alzheimer’s back in 2011, but this was rejected on the grounds that the study involved too many variables.
“People are not easily going to change their minds about these things; they don’t want to be told they’re wrong, I get that,” Bredesen says. “And of course, also, because you spend your whole career with this idea that a drug is going to come someday.
“Typically, the experts who are far along in their careers will never believe it, no matter what we publish. So, it’s really the students of the experts that we’re interested in – they’re the ones who are a little more open-minded.
“Over time, they’ll be the ones that actually bring this into practice.”
The researchers were eventually granted approval to explore their hypothesis in 2019. The study’s promising findings indicate that a broader, personalised approach to treatment has the potential not merely to slow the effects of dementia, but actually reverse them. Bredesen is optimistic that the research could mean life-changing treatments for dementia patients in the future.
“Fundamentally, it’s not one thing that’s causing [Alzheimer’s],” he says. “And therefore, we need to take a very different approach. We need to look deeply into this, analyse it, and then target those things.
“When we do that, the results are really spectacular.”