So, another week and another Alzheimer’s breakthrough is gracing the headlines of the papers. The research in question was issued in Nature last week with the title of “The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease”. The paper, a formal write-up of lab work and clinical trials, describes startling results of a new drug designed to destroy the characteristic brain structures seen in the disease.
Needless to say the drug was successful – so successful in fact that the decline in brain function in actual Alzheimer’s patients was measurably slowed after a year on the drug. Not only is the prospect of a new drug to treat Alzheimer’s an exciting and important one, this research also holds significant promise for developing and extending our understanding of the disease.
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To understand what aducanumab does and how, you’ll need a bit of background on what a brain affected by Alzheimer’s looks like down the microscope – what researchers call the ‘neuropathology’ of the disease. Two unusual structures can be seen throughout an Alzheimer’s brain; tangles of protein inside neurons, and dense plaques in the spaces in between.
It’s long been theorised that the formation of plaques was the root cause of Alzheimer’s symptoms, while the tangles were just a by-product of the damage they caused. This idea, known as the ‘amyloid hypothesis’ (after beta-amyloid, the protein which makes up the plaques) has been fundamental to our understanding of Alzheimer’s for over ten years. During this time endless attempts have been made to treat the disease using drugs that target the beta-amyloid plaques. These attempts have been largely unsuccessful – until aducanumab.
Aducanumab is an antibody – it can target specific shapes on the surface of a beta amyloid plaque in the same way your immune system recognises bacteria. The antibodies in the new drug bind to the surface of the plaque and engage the immune system to clear the plaques from the brain. When the researchers demonstrated how well this worked using genetically modified mice, they started trials on humans.
The clinical trials, carried out with 125 early-stage Alzheimer’s patients over one year, showed results similar to the results seen in the mice; there was a reduction in the number of beta amyloid plaques in the patient’s brains. What’s even more exciting than that is the news that across several tests of cognitive impairment the patients who were treated with the drug showed a slowing of the mental decline normally seen in disease patients. While this seems hugely encouraging for aducanumab, the authors of the study make it very clear that we shouldn’t get too excited – their sample size of patients was too small to say for sure whether the drug is actually effective in slowing Alzheimer’s disease, this is merely an indication that aducanumab is worth further investigation.
While we shouldn’t take these reports of slowed decline as evidence that a new Alzheimer’s treatment is around the corner, this research is still hugely important. The work establishes a link between the destruction of beta-amyloid plaques and a change in the symptoms of Alzheimer’s patients for the first time. This lends credence to the idea that the key to treating Alzheimer’s patients lies in the removal of beta-amyloid plaques, just as the amyloid hypothesis suggested so long ago.