May 01 2020

Nanotechnology to Treat Alzheimer’s Disease

This is a very cool study, with the massive caveat that it is extremely preliminary – but scientists have concluded an in vitro study of nanodevices that can reduce one of the pathological changes thought to be a significant cause of Alzheimer’s disease. This has to be put into context, but let me first describe what they did.

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the brain diffusely. Little by little brain cells die, the brain atrophies, and cognitive ability slowly declines causing dementia. The disease affects about 10% of people over 65, producing a huge burden on individuals, families, and society. As our population ages, it is becoming even more prevalent. There is extensive research on how Alzheimer’s disease progresses, looking for clues that might lead to an effective treatment. However, it has proven a tough nut to crack. We have many clues, but nothing that has lead to a treatment that can prevent, stall, or reverse the neurodegeneration. It is, in short, a complex disease.

One piece of this complex puzzle is the β-amyloid peptide (Aβ), which is a breakdown product of an amyloid protein precursor. The simple version is that this peptide is normally cleared from brain cells as a waste product, but in some individuals it is not sufficiently cleared and there is enough hanging around to form conglomerations or clumps of the protein. These clumps form plaques, which are a major pathological sign of AD. However, the picture is more complex than that. The amount of plaques in the brain don’t necessarily correlate with the severity of the dementia in AD, so it is clearly not the whole picture. More recent studies have found:

Substantial evidence now indicates that the solubility of Aβ, and the quantity of Aβ in different pools, may be more closely related to disease state. The composition of these pools of Aβ reflects different populations of amyloid deposits, and has definite correlates with the clinical status of the patient.

There are also pathological processes in AD that are not related to amyloid plaques, so again we are only dealing with part of the picture here. Still, researchers have been looking for ways to prevent plaque formation as a possible way to slow, stop, or even reverse AD. So far nothing has led to an approved treatment. (Current treatments for AD are only symptomatic.)

This brings us to the new research, which is exploring a fairly high tech approach to the problem – using the combination of nanodevices and engineered antibodies to soak up the Aβ peptides and eliminate them before they have a chance to clump into the amyloid plaques. The device is a nanoscale particle that is porous to create a lot of surface area. The surface is then coated with antibodies that bind to the Aβ peptides. One nanoparticle can therefore bind many peptides, keeping them from clumping together, and then get flushed out of the system.  They tested the devices and found:

At CNM, the scientists tested the effectiveness of the devices by comparing how the peptides behaved in the absence and presence of the nanodevices. Using in vitro transmission electron microscopy (TEM), they observed a notable decline in peptide aggregation in the presence of the nanodevices.

The devices reduced Aβ peptides by 90%. This is just a study of the effects of the nanodevices in a dish, really just a proof of concept.  They did what they were supposed to do, which is a great first step. They also report, however:

The in vivo experiments — experiments that took place in living cells — performed by Lee and his collaborators showed that the nanodevices are nontoxic to cells. They also tested the effectiveness of the devices in the brains of mice with Alzheimer’s, demonstrating around 30 percent suppression of plaque formation in brains containing the nanodevices compared to control brains.  The research on mice was conducted at KIST and KAIST in South Korea with appropriate government approvals.

So we have some in vitro studies and preliminary animal studies of safety and effectiveness.  This is still in the very early stages of testing. We need to replicate and expand the animal data, and then if everything is looking good, go through the decade long process of human testing. If all goes well we are probably looking at 10-15 years for an approved treatment. However, with such new medical technology thing rarely all go well. I have also been reading about AD breakthroughs that look promising for decades, and you will notice none of them have lead to an effective treatment for AD. Still, every advance like this is encouraging. We need to keep rolling those dice and hopefully one time we will hit upon an actual effective treatment.

This story also highlights, not just the state of AD research, but the fact that we do appear to be on the cusp of new treatment strategies in medicine. The ability to control the properties of devices at the nanoscale, which is the scale of cells and many biological functions, at least opens the door to the possibility of nanomachines that can treat disease and degeneration. We also continue our advance in molecular technology – controlling proteins, genes, antibodies, receptors, and other biological components. This study caught my attention because it combines both of these technological approaches – nanodevices and antibodies.

We are going beyond pharmacology. We already are seeing a wave of monoclonal antibody treatments getting approved. Some of these are proving more effective with fewer side effects than any drug. It is a real advance, and it is here now. We are also seeing immune treatments for cancer making a significant difference. For me this also shows the real delay in the application of basic science research. Some of these treatments that are just now coming online I learned about in the 1990s. This may be creating the curious situation that by the time breakthroughs get to the point of application, they are old news. The press has already moved on to the new basic science studies that may or may not pan out in 20 years.

But let’s not neglect to notice the significant scientific medical advances we are actually making, and that are in use today. Gene therapy, immunomodulation, and monoclonal antibodies my be old ideas, but they are new treatments, and they are transforming medicine in a good way.


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