Get those plaques out early!

I think it's amazing how researchers have shown that you can actually clean the brain of those amyloid plaques we see in Alzheimer's disease.  This has been done with monoclonal antibodies that consume and dispose of the pesky peptides.  But what is the role of the plaques?  Are they a part of the disease process, such that removing them will stop the disease?  Or are they perhaps part of the body's defense against a pathogen causing the disease?  Or are they there for some other reason?

We have discovered that some treatments removing the plaques appear to slow, but certainly not stop the progress of the disease.  Others get rid of the plaques, but the disease continues.  Are there better approaches to removing the plaques that might more reliably improve memory and cognition?

One thought that comes up often is that we need to attack the disease earlier in its progress.  Generally, participants in drug trials are already showing evidence of cognitive impairment.  But, as we discussed in Beating the Dementia Monster, the disease has been in progress for at least 15 years before the first symptoms appear.  And so it's common to read a proposal that we need to start treatments much earlier.  But I haven't seen much success in that area ... until recently.

"Dominantly Inherited Alzheimer's disease" (DIAN) refers to what we called in Beating the Dementia Monster "young onset" Alzheimer's disease.  (We avoid the term "early onset" Alzheimer's disease so as not to confuse it with "early stage" Alzheimer's disease.)  We described the origin of the disease, specifically in the presence of three, relatively rare genes.  These are PSEN1, PSEN2, and APP.  When one of these genes is present in someone's genome, and if it is dominant over its recessive partner, the person carrying the gene is almost certain to develop the disease -- and develop it at a young age.  Usually, this is in the decade of the 50's, but it could even be in the person's 30's.  

This means that, through genetic testing, we can identify people at a very young age -- even from their childhood -- who are very likely to develop the disease .  This is more than that 15 years before those first symptoms.  So, if we can now identify those people, how about starting to administer the treatment at the very beginning of the disease process -- or even before it begins?

That's what they're doing at Washington University, St. Louis.  In a series of three trials, they are trying to stop the disease before it begins or else to interfere with it's progress once it has begun.  The first trial is using the monoclonal antibody "remternetug" to remove the plaques.  They are enrolling participants as young as 18, perhaps 25 years before the expected onset of the disease.  Expectations regarding onset are based on what happened with the participants' parents. 

According to the Washington University web site, "the trial is part of the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (Knight Family DIAN-TU), a clinical trials platform designed to find medicines to prevent or treat Alzheimer’s disease."  ("TU" signifies "trial unit.")

The researchers hope to enroll 240 participants in the prevention trial, and the participants will receive the antibody treatments for two years.  They plan to start reporting results relatively soon after the first participants complete their two years.  They will be looking for evidence they have obstructed the disease, although it will be way too early to see if the treatment affects memory and cognition.  That will take years of follow up.

So is this it?  Is this how we will establish a pharmaceutical resolution to this terrible disease?  We won't know anytime soon.  If it is effective, and if it's equally effective with other "flavors" of the disease, it will still be a project to determine who will benefit from it.  Certainly the presence of the ApoE4 gene (the one they look for in 23&ME) in someone's genome would indicate this is a promising treatment.  And there are at least 30 other genes that predispose someone to the disease.  So genetic profile will be a starting place.  But don't be holding your breath for any near-term benefit.