Incredible ‘Living’ Alzheimer’s Implant Clears Mouse Brains of Toxic Junk

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Alzheimer’s may be the cruelest of brain diseases.

Decades before the first signs of dementia strike, toxic protein clumps called amyloid plaques have been slowly, insidiously building up in the brain. The plaques clog the brain’s waste disposal system and wreak havoc on the delicate molecular machinery that underlies our memories, our history, our personality.

By the time deceptively benign senile moments turn into full-blown dementia, it’s too late to treat.

implant-to-prevent-alzheimers-disease-6Our helplessness against dementia is especially frustrating, because scientists know how to slow it down if caught early. The answer is passive immunization. Just like vaccines stimulate the body to produce antibodies and protect against various infections, we can introduce antibodies that prevent amyloid proteins from clumping.

In theory, these guardians would circulate the aging brain and protect it from amyloid buildup, especially in people with genetic mutations that increase their chance of developing dementia.

Yet clinical trials using antibody injections have consistently failed. The reasons are many, but one stands out: most antibody injections need to be given at extremely high doses to be moderately effective. And in pharmacology, the dose makes the poison.

With repeated high dose injections, therapeutic anti-amyloid antibodies can cause severe side effects. Unlike small molecule drugs, antibodies are huge proteins that throw our bodies’ immune systems into red alert. Immune cells deploy, seeking out and destroying the therapeutic antibodies long before they reach the brain.

Then there are off-target effects. Once inside the brain, antibodies can in some cases tamper with the brain’s normal functioning by disrupting the normal chatter between neurons.

The solution to these side effects is deceptively simple: forget bombarding the brain with large antibody doses. Instead, deliver the therapeutics in a slow and smooth trickle. But how?

A team at the EPFL in Lausanne, Switzerland may have an answer. A bioactive capsule—about an inch long and packed with genetically engineered cells that steadily pump out anti-amyloid antibodies—is implanted under the skin of susceptible patients long before the first signs of cognitive decline strike.

In a proof-of-concept study published this month in Brain, the team tested their capsule in two transgenic Alzheimer’s mouse models engineered to produce abnormal amounts of human amyloid proteins in the brain.

When implanted into young mice long before symptoms appeared, the encapsulated cells steadily synthesized anti-amyloid antibodies for 10 months and significantly reduced pathological signs of protein clumps in the brain later in life.

A Living Antibody Factory

The capsule — a one-of-a-kind bioengineering feat — is based on previous work from the same lab back in 2014.

The team started with genetic cloning. They introduced genes that encode a type of anti-amyloid antibody, called MAb-11, into a virus.

Next, they infected immortalized mouse cells in a dish with these viruses. The cells took up the extra genes and integrated them into their own genome. Before long, the cells started secreting MAb-11.

The problem then is getting the cells into a mouse without stimulating the recipient’s immune system. That’s where the capsule comes in.

Made from biocompatible porous material that lets nutrients in and antibodies out, the inch-long nugget is seamlessly sealed tight using ultrasonic waves. The capsule has an integrated port that allows scientists to directly inject antibody-producing cells into the inner chamber, where they take root in the chamber’s hydrogel filling.

Because the capsule shields the precious cells from the recipient’s immune system, these antibody-producing cells can live inside the host for months — a highly efficient, living antibody factory right inside the body.

Image credit: EPFL

Image credit: EPFL

Destroying Plaques

Capsules in hand, the team next implanted them under the skin of two different mouse models of Alzheimer’s disease. Both models were genetically engineered to have mutations often seen in humans at risk for the disease.

To start out, the scientists wanted to see if they could delay the pathological symptoms of Alzheimer’s after the plaques had already formed.

Nine months after implantation, scientists found that the cells had expanded to fill up the capsule. The cells looked healthy and were hard at work, constantly secreting MAb-11 into the bloodstream.

implant-to-prevent-alzheimers-disease-2

Image credit: EPFL

When scientists looked into the mice’s brains, they found that MAb-11 had tagged onto the amyloid proteins, sending out a warning call to the local immune system. Further, they saw microglia — specialized immune cells that patrol the brain and gobble up waste — had burst into activity, engulfing toxic amyloid clumps much more efficiently than microglia from control mice.

As a result, the antibodies significantly reduced the number and size of amyloid plaques throughout the brain. Encouraged, the team next asked the harder question: can the capsule prevent toxic protein buildup before symptoms start?

The result was a striking yes.

When the scientists started treatment 6 months before mice first showed any telltale signs of amyloid plaques, they found MAb-11 reduced toxic plaque buildup by roughly 95% (compared to control mice) ten months after implantation.

Long Road Ahead

The results are undoubtedly encouraging.

Because the cells used to produce antibodies are immortalized, they can be grown at a much more rapid pace than any other type of cells, easily scaling up production. And because the capsule protects the cells from the host’s immune system, in theory the treatment could be given to anyone without risk of rejection.

That said, it’ll be a long road before the capsule reaches market.

For one, scientists found that some mice eventually developed resistance. Bit by bit, their immune systems recognized MAb-11 as an invader and produced antibodies of their own to wipe out the therapeutic protein. Although simultaneous treatment with anti-CD4 (a protein that blocks the anti-drug response) helped, this expensive fix isn’t really practical for long-term use in human patients.

Like a cat-and-mouse game, researchers may have to switch from MAb-11 to another type of anti-amyloid antibody every few months to avoid tolerance.

Then there’s this: the amount of amyloid plaques in the brain doesn’t always correlate with memory decline. Unfortunately, the authors didn’t run their capsule-implanted mice through memory tests, and so (although very likely) it’s hard to say whether the treatment actually slowed memory loss in these mice.

Alzheimer’s disease is notorious for its “graveyard of drugs” — drug candidates that initially showed promise, but ultimately failed in humans.

Although just the first step, this study solves one of the thorniest issues plagueing the disease — prevention. The microcapsule offers a way to begin treatment early. Instead of passively reacting to the toxic protein buildup cascade, we may be able to nip the process in the bud.

But perhaps the most titillating result is this: many neurodegenerative diseases —Parkinson’s, Huntington’s, ALS (of the ice bucket challenge fame) — all involve a buildup of toxic proteins. The cell-encapsulating device could, in theory, be a universal bullet against some of the most difficult brain disorders of our time.

The study may just be the first step, but it’s one hell of a big one.

Original Post

"Incredible ‘Living’ Alzheimer’s Implant Clears Mouse Brains of Toxic Junk"

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This is amazing and very good news for Alzheimer's patients [and probably would help other mental illness suffers].

Though, if our politicians get out of bed with corporate farms, chemical companies and Wall Street, giving corporate farms and food companies and those whose investments depend on them card blanc with the American food supply and our environment, there would be less Alzheimer's patients in the first place, because a virtually man-made chemical-free diet of healthy foods that have not been denatured and saturated with chemicals, toxins, medicines[synthetic medicines], animal hormones[veterinary medicines (which are synthetic man-made chemical for animals)], the human body would already be doing what this "implant" does to avoid Alzheimer's naturally.

Political corruption has taken our science so far away from nature at this point, that "Western Science" really is no more than atool for Big Agri/Corporate Farms, Big Business, Big Oil, Big Pharma, Wall Street and Big Banks, that is being used to come up with with ban-aids cover all the damage, illness, disease and environmental destruction they cause and profit from.

  I know but I can't help but hear in the back of my mind...the sign of the beast image that religious propaganda STUMPED in my head.  I remember when they first introduced the "chip" for animals.  It was deemed sign of the beast.  So whenever I hear the word "implant" my brain goes there.  Over the years, I just become so skeptical about doctors/pharmacutical companies....and their motives...and hidden agendas.  If this is on the up and up, it could be a fantastic breakthrough for those who suffers from Alzheimer's and dementia.  Yet I remember horror movies where the mad scientists is shown to always have the anti-dote before he uses the poison.  And life mirrors art so in that I think there are cures all over the place, but scientists, doctors and those drug companies can't make money off of "cures" ...so they gon go the longer route:  treatment.  And the folks who pays?  Are us.  Cuz sometimes the treatment is worse than the condition.    Just sayin.   But!  

Kocolicious posted:

  I know but I can't help but hear in the back of my mind...the sign of the beast image that religious propaganda STUMPED in my head.  I remember when they first introduced the "chip" for animals.  It was deemed sign of the beast.  So whenever I hear the word "implant" my brain goes there.  Over the years, I just become so skeptical about doctors/pharmacutical companies....and their motives...and hidden agendas.  If this is on the up and up, it could be a fantastic breakthrough for those who suffers from Alzheimer's and dementia.  Yet I remember horror movies where the mad scientists is shown to always have the anti-dote before he uses the poison.  And life mirrors art so in that I think there are cures all over the place, but scientists, doctors and those drug companies can't make money off of "cures" ...so they gon go the longer route:  treatment.  And the folks who pays?  Are us.  Cuz sometimes the treatment is worse than the condition.    Just sayin.   But!  

Hey, I understand, but I think the "beast" has already come and is hiding in plane sight; it's already here, and has been here for a long time; it's money; the "Mark of the Beast" is the seal on money, and "seal/mark" in everyone's hand" is the seal on the money in everyone's hand or on everyone's mind.

 

Revelation 13:

  1. And he causeth all, both small and great, rich and poor, free and bond,to receive a mark in their right hand, or in their foreheads:
  2. And that no man might buy or sell, save he that had the mark, or the name of the beast, or the number of his name.

 

 

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