New Study Explains Why So Many Alzheimer's Clinical Trials Failed

“We show that a vicious positive feedback loop exists in which beta-amyloid drives its own production,” said senior author Richard Killick from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN). 

Killick continued and hinted that this could be why 15 years of innovative and promising Alzheimer's drugs have failed during clinical trials. 

“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," he said.

The King's College team said while the initial discovery is upsetting for any researcher dedicated to destroying beta-amyloids, the findings are a step forward rather than back. 

“Our work uncovers the intimate link between synapse loss and beta-amyloid in the earliest stages of Alzheimer’s disease,” said lead author Christina Elliott from the IoPPN. “This is a major step forward in our understanding of the disease and highlights the importance of early therapeutic intervention.”

Finding a drug to break the cycle

However, not all Alzheimer's drugs are nullified according to the researchers. The team identified a drug called fasudil -- one already being used in Asia for strokes. 

“Importantly, our work has shown that we may already be in a position to block the feedback loop with a drug called fasudil which is already used in Japan and China for stroke.” said Killick. “We have convincingly shown that fasudil can protect synapses and memory in animal models of Alzheimer’s, and at the same time reduces the amount of beta-amyloid in the brain.”

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The animal models in question are mice. The mice have been engineered to develop large deposits of beta-amyloid in their brains, with the deposits growing rapidly as they age. However, the King's College team discovered that just two weeks of treatment with fasudil drastically reduced the beta-amyloid deposits. 

Professor Dag Aarsland from the IoPPN said “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. We now need to move this forward to a clinical trial in people with early stage Alzheimer’s disease as soon as possible."

The researchers are now wanting to run a trial in early stage sufferers of Alzheimer's to see how fasudil improves their brain health and stops the decline of brain function.