- Scientists at Washington University were able to reduce the levels of Alzheimer’s plaques by half in mice using a new antibody treatment
- Pharmaceutical companies have been trialing antibody-based Alzheimer’s treatments in recent years, but, so far, none has made it past the clinic
- The new treatment targets a small part of the plagues proteins, but lead to the destruction of the whole thing
- The antibody did so in mice without the side effects that worry scientists most
Certain antibodies may be able to remove Alzheimer’s plaques from the brain, according to new research carried about in mice.
As much as 20 years before the symptoms of Alzheimer’s set in, people with the disease begin to develop amyloid beta plaques that build up in the brain and, scientists believe, interfere with neural signals to cause cognitive and memory losses.
But researchers at Washington University School of Medicine have developed an antibody that can remove the proteins these plaques are made of altogether, according to their new research.
Several recent clinical trials have tried to use antibodies to target the plaques, but none have gotten past these trial phases, and many treatments have come with unsustainable side effects.
The new approach may offer a way around these side effects and stop Alzheimer’s plaques before its heart-breaking symptoms begin, the researchers hope.
Antibodies (red) target and bind to a smaller protein within the amyloid beta proteins plaques (blue) that clog the brains of Alzheimer’s sufferers. The antibody clears the whole protein away
Despite the hundreds of millions of dollars spent on Alzheimer’s disease each year, we are still largely helpless against the disease once it sets in.
We now know some of the key genetics behind the disease, as well as the key biological marker of it in the brain: the amyloid beta protein plaques.
These plaques are composed of pieces of protein that come from the fatty membranes that coat neuron cells.
Normally, if these fragments break off, naturally occurring enzymes can break them so that they do not have a chance to turn into a clump.
For whatever reason, this natural waste removal does not seem to happen in the brains of people with Alzheimer’s.Scientists suspect that as these proteins build up and stick together – either wrapped around neurons or roaming freely through the brain – they block the electrical signals fired across the synapses different parts of the brain try to communicate with one another.
Academic researchers as well as pharmaceutical and biotech companies have looked to antibodies to target these plaques, but, recently, pharmaceutical giant Eli Lily had to drop the most promising drug it had been developing with this approach.
Antibodies have specific identities that make them suited to fight particular invaders, or pathogens, in the blood.
The new study experimented with an antibody that matches not the amyloid beta proteins themselves, but a smaller protein contained within them, called APOE.
Certain variations of the gene for APOE are the single greatest genetic predictor for Alzheimer as well, and the same research team had previously found that they could mitigate some of the damage done by amyloid beta proteins by aiming treatment at the APOE protein.
But, ultimately, the bigger goal in Alzheimer’s research is to stop, undo or even prevent the development of the plaques in order to stop Alzheimer’s.
So the team designed an experiment to see if they could use APOE for a search-and-destroy purpose, rather than just a containment one.
They tested a number of antibodies that were good fits for human APOE, which they had given to mice, along with Alzheimer’s plaques.
Once the antibodies made it to their target proteins, they acted like beacons, calling the attention of other immune cells to come joint the attack against small protein and the whole vicious protein it sat inside.
The performance of one of these antibodies was particularly impressive.
Over the course of six weeks, the level of amyloid beta proteins in the mice treated with HAE-4 fell to half what they had been prior to treatment.
The antibody was able to pick out the APOE protein, and, when it dislodged it, take the rest of the larger amyloid protein with it.
The researchers had worried that, because APOE plays an important role in eliminating fats and cholesterol from the blood stream, attacking the protein could have collateral damage for its helpful purpose too.
But, ‘it turns out that the APOE in the plaques has a different structure than the form of APOE found in the blood,’ senior study author Dr David Holtzman said.
‘The HAE-4 antibody recognized only the form found attached to the plaques in the brain,’ which meant it would not target the helpful blood proteins.
It also did not seem to cause the same inflammation that other antibodies had induced by targeting the larger amyloid proteins.
‘The anti-amyloid antibodies are going to be binding to most of the molecules that are in the plaque, but the anti-APOE antibody would target just a very small component of the plaque,’ said Dr Holtzman.
‘This means we may find less immune activation, and we might not see the unwelcome side effects,’ he added.
If the treatment works as well in humans as it did in the experiments in mice, it may well provide a more effective and safe key therapy those whose brains ‘build up amyloid over many years and…just can’t get rid of it,’ said Dr Holtzman.