Researchers from Washington Medical School have used an antibody to target just a small component of amyloid plaque in Alzheimer’s, and avoided the failings of other antibody drugs which often resulted in bleeds and strokes.
Resolutely ignoring all the research on the connection between disturbances in the gut microbiome leading to the immune system attacking the areas in the brain around amyloid plaque in cases of Alzheimer’s and dementia, researchers have continued to look for drugs and ‘anti-bodies’ that could attack the plaque and break it up and/or dissolve it.
But there’s a problem: to date such drugs prompted a significant increase in localised inflammation and a by-product (ARIA), where the plaque was close to arteries, leading to bleeds and strokes.
Not to be outdone, researchers from Washington University School of Medicine in St Louis have developed an antibody that removes amyloid plaque from brain tissue around blood vessels without the inflammation and bleeds. Well, at least in mice, anyway.
This lack of inflammation is because the antibody only attacks a minor component of the plaque, called Apoliprotein E (APOE).
David Holtzman, MD, the head of the Department of Neurology said, “Each of the antibodies that removes amyloid plaques in clinical trials is a little different, but they all have this problem, to a greater or lesser degree. We’ve taken a different approach by targeting APOE, and it seems to be effective at removing amyloid from both the brain tissue and the blood vessels, while avoiding this potentially dangerous side effect.”
ARIA when present indicates swelling or bleeding in the brain caused by inflammation, and can lead to headaches, confusion and even seizures. Hitherto 20% of participants developed ARIA.
ARIA seems to be the result of an overenthusiastic inflammatory response. In this trial, the researchers used an antibody called HAE-4 that targets a specific form of human APOE that is found only sparsely in amyloid plaque. Significant improvement was seen in the mice within 8 weeks.
- Monica Xiong, Hong Jiang, et al; APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function. Science Translational Medicine 17 Feb 2021