A new drug that targets toxic amyloid proteins in the brain - one of the main hallmarks of Alzheimer's disease - has produced such promising results in a small clinical trial, it's now being assessed in two larger trials involving 3,500 patients.
If the drug, which is taken in tablet form, can be proven to slow the devastating mental decline that's associated with Alzheimer's, it could be the first treatment to enter the market in more than 10 years.
Developed by pharmaceutical giant Merck Labs, the new drug has cleared a Phase I clinical trial involving 32 Alzheimer's patients. The trial was primarily focused on assessing the drug's safety, but in the process, it appeared to be blocking the production of toxic amyloid proteins.
In the brains of people with Alzheimer's disease, amyloid proteins accumulate and clump up, sitting between the neurons as dense, toxic clusters called plaques.
Together with neurofibrillary tangles - the other key indicator of the disease - they cause disruptions to the transportation of essential nutrients around the brain, which is thought to bring on the cognitive decline and memory loss associated with Alzheimer's disease.
While scientists have been debating for years over which plays the bigger role in driving the onset of Alzheimer's - amyloid plaques or neurofibrillary tangles - being able to eliminate one could either slow the progression of the disease, or at least help us narrow down the real culprit.
If initial results from the new drug - called Verubecestat - can be replicated in larger, more long-term Phase III clinical trials, we could have a way of stopping these plaques from forming altogether.
"Today there are very limited therapeutic options available for people with Alzheimer's disease," lead researcher Matt Kennedy told Hannah Devlin at The Guardian. "[T]hose that exist provide only short-term improvement to the cognitive and functional symptoms. They do not directly target the underlying disease processes."
Neuroscientist John Hardy from University College London, who was not involved in the development of the drug, says the results are looking very promising so far.
"People are excited," he said. "This is a very nice drug, and I'm sure Merck are feeling very pleased with themselves."
Hardy was the first to identify the link between amyloid proteins and Alzheimer's disease.
The Phase 1 clinical trial that was just completed involved giving 32 patients with early stage Alzheimer's disease the drug every day for seven days. Healthy volunteers were also given the drug for up to two weeks as a control.
The drug passed the test in terms of safety - no adverse side effects were recorded - but there was something perhaps even more exciting in the results.
The trial was too short to see changes in amyloid plaque build-up in brain scans, but samples of fluid surrounding the brain revealed that compounds known to form abnormal amyloid proteins had been reduced.
Verubecestat has been designed to target the enzyme BACE1, and block its activity. BACE1 appears to facilitate the production of amyloid proteins by cutting molecules called amyloid precursor proteins (APP) into pieces, which go on to form sticky amyloid proteins.
While BACE1-inhibiting drugs have been developed in the past, this is the first that appears to work with no major side effects - and that's a big step forward for the development of an amyloid-targetting treatment.
"This is the first detailed report of what a BACE inhibitor does in humans," Alzheimer's researcher Dennis Selkoe from Harvard Medical School, who was not involved in the study, told Scientific American.
"The good news is they didn't see evidence so far of any of the side effects we're concerned about with BACE inhibition."
The Merck team has already begun two Phase III clinical trials with the drug, one involving 2,000 patients with mild to moderate Alzheimer's disease, and one with 1,500 'prodromal' Alzheimer's patients - meaning they're in the earliest stage of the disease. Each will run for at least 18 months.
The results of the first trial are expected in July 2017, and the second, some time in 2019.
So we now have to sit and wait some more to see if the drug can live up to its promise. But, as Hardy told The Guardian, "Conveying some excitement isn't the wrong thing to do in this case."
The results of the Phase 1 clinical trial, and earlier animal trials, are reported in Science Translational Medicine.