New implant shown to destroy protein plaques in Alzheimer’s disease


Following closely in the wake of a breakthrough in our understanding of the way amyloid-beta (Aβ) and tau proteins spread through the brain in Alzheimer’s disease, a new study from the EPFL in Lausanne has shed light from another angle on what’s going on under the hood. Experiments with mice have shown that a tiny, flat transdermal implant can deliver precisely engineered antibodies that clear amyloid-beta plaques from mouse brains. They’re calling it “passive immunization,” and it could be the next step on the path to a cure.

The indwelling device itself is a little flat capsule-shaped thing, built to hold myoblasts suspended in a protective hydrogel between two porous membranes sealed together by a tiny frame. Those myoblasts can interact with the surrounding tissue through the permeable membrane. They’re engineered to sit under the skin and produce specific antibodies which can breach the blood-brain barrier, bind to the amyloid-beta proteins in mouse brains, and tag them for destruction and disposal by the mouse’s own immune system. In two different mouse Alzheimer’s models, these transdermal implants dramatically reduced the Aβ plaque load.

During the experiment, some 39 weeks after implantation, the EPFL researchers saw that the myoblasts had great survival rates and were calmly churning out anti-amyloid antibodies at a rate sufficient to halt their deposition and clear existing plaques from the mouse brains. The mice laid down new vasculature to nourish the myoblasts, and even though the engineered antibodies contained human genetic material, they and their parent myoblasts were preserved from wholesale immune attack by the porous containing membrane.

Furthermore, the researchers observed reduced phosphorylation (activation) of tau protein, the other prime offender as far as current Alzheimer’s research can tell. That even got the attention of the Kurzweil singularity crowd, which eagerly anticipates clinical advances capable of stalling the heretofore-inevitable creep of aging.

The fact remains that just because these protein plaques are understood to be the primary pathology doesn’t mean removing the plaques will be a cure for Alzheimer’s disease or anything else. Giving in to breathless hype is the surest path to disappointment, especially when what we have is one team working with a couple of nonhuman disease models.

We don’t know whether removing the plaques will alleviate the symptoms of Alzheimer’s, especially in light of the fact that amyloid plaques accumulate as everyone ages, not just people who have Alzheimer’s. We don’t know what other parts of the body’s amazingly intricate proteome will have functional regions that these antibodies could bind to, nor what will have to go wrong for us to find out. Fiddling with the immune system tends to lead to imbalances and inflammation –and lately, more and more diseases and syndromes are being linked with the immune component of their pathology. The moral of this story is that we need to tread carefully with regard to immune function.

Nevertheless, the way these devices perform led the Lausanne team to conclude that this is an important breakthrough in neurodegenerative disorders associated with protein misfolding or aggregation. Transdermal implants are much less invasive than the current state of the anti-Aβ-antibody treatment process, which involves frequent injections of antibodies that end up incurring an immune response just because of the relatively huge volume of immunogenic particles. In their Brain writeup, the team declared Alzheimer’s, Parkinson’s, frontotemporal dementia and ALS to be fair game for targeting by passive immunization.

Their next step? Scaling up the implant, tweaking the antibodies so they’re better at getting through to the brain, and moving forward to human clinical trials.


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