One in 10 US adults over the age of 65 have Alzheimer’s and one in three seniors will die from the disease or another form of dementia. Yet, there is no cure available and there is nothing promising in the pipeline – though scientists have recently begun experimenting with “brain pacemakers” and young blood transplants. Now, a team of researchers at King’s College London (KCL) think they might know why exactly that is.
The vast majority of drugs designed to slow or reverse the progression of Alzheimer’s target the protein beta-amyloid, whose overproduction is very closely tied to the onset of the disease. This is because it attacks and damages the connections between the brain’s nerve cells (synapses), which can cause memory problems, dementia, and even death.
What was unknown until now is that during this synapse-destroying process, the nerve cells produce more of the protein beta-amyloid, exacerbating the problem and producing a savage feedback loop where more and more synapses get damaged. The researchers described their discovery in a paper published in the journal Translational Psychiatry.
“We think that once this feedback loop gets out of control it is too late for drugs which target beta-amyloid to be effective, and this could explain why so many Alzheimer’s drug trials have failed,” Richard Killick, senior author and lecturer at the Institute of Psychiatry, Psychology & Neuroscience (KCL), said in a statement.
But that’s not all. The researchers have also identified a drug they think could be used to break the cycle.
Fasudil is clinically approved and is already used in Japan and China to treat stroke patients. Experiments in mice have shown that it is able to protect the brain’s synapses and memory while reducing levels of beta-amyloid.
So, how does it work? Rather than target beta-amyloid, the drug targets Dkk1, another protein that has been identified as an important factor in the development of Alzheimer’s in Killick’s previous work. Dkk1, Killick and co. hypothesize, stimulates the production of beta-amyloid. This would make it an essential player in the feedback loop. Stop Dkk1 and you can stop the production of beta-amyloid, thereby stopping the destruction of the brain’s synapses.
Fasudil has already been tested in mice genetically engineered to produce an excess of beta-amyloid in their brains as they matured. After two weeks of treatment, the deposits of beta-amyloid had shrunk dramatically.
“As well as being a safe drug, fasudil appears to enter the brain in sufficient quantity to potentially be an effective treatment against beta-amyloid,” said Dag Aarsland, a professor also at the Institute of Psychiatry, Psychology & Neuroscience.
It’s proved successful in mice but that doesn’t necessarily mean those same results will be replicated in humans. Enter the next stage: clinical trials.
“We now need to move this forward to a clinical trial in people with early-stage Alzheimer’s disease as soon as possible,” Aarsland added.