Another nose spray for Alzheimer's disease? It's worth a try.

My friend Paul, high school classmate from many, many years ago, sent me an article about use of the antibiotic rifampicin to prevent or treat Alzheimer's disease.  The article talked about administering the antibiotic to the brain using a nasal spray.  Apparently, rifampicin is protective of the brain in ways other than by being an antibiotic.  This has actually been known for several years, as explained in this article from 2018.  But the trick is to get it past the blood-brain barrier (BBB).  Another trick is to prevent the liver damage that rifampicin is famous for.

Why a nasal spray?  To get around the BBB I presume.  If you read Beating the Dementia Monster, you know that I participated in a trial of the use of nasal insulin.  Twice a day for 18 months I squirted insulin into my nose so that it could be transported directly into the brain without going through the blood stream.  The insulin followed the path of the olfactory nerve into my brain.  The BBB was not an issue with insulin, since it must get into the brain anyway.  They simply wanted a higher level of insulin in the brain than in the blood flow servicing the rest of the body.  

But it's a little harder for rifampicin, and it won't pass easily into the brain from the blood stream.  So going through the nose bypasses the BBB.  (I wrote previously about the higher levels of dementia among people who live near freeways or in areas of high air pollution.  It's believed that pollutants are entering the brain via the pathway of the olfactory nerve.)

The article that Paul sent me is here.  It is about starting drug trials to find out if this will work.  The plan is to combine rifampicin with resveratrol and have people squirt that in their noses.  If you read Beating the Dementia Monster, you know that we find resveratrol in red wine, and it's thought to support brain health when taken in wine.  (As a supplement it seems to be ineffective.)  But, at least from what I read, the function of the resveratrol with the rifampicin is to prevent liver damage.  How that will happen, I don't know.

But, so far, it all seems to work great in mice. 

I don't know if they will be drawing on anything from the insulin study, but that study was bedeviled by problems with the design of the applicator.  They redesigned it several times, but after they told me the trial had failed to produce improved cognition, I read that there was still doubt about how well the applicator delivered the insulin.  Hopefully, they won't have similar problems with a rifampicin trial.

So what is this antibiotic going to do in the brain?  Apparently in mice it has mitigated the rise of amyloid plaques and defective tau proteins.  It has also prompted the production of the brain-derived neurotrophic factor (BDNF).  In Beating the Dementia Monster, we explained that BDNF is generated in aerobic exercise and in intermittent fasting, and it can both repair damaged neurons and prompt stem cells form new neurons.  

The 2018 research found that rifampicin conducts "inhibitory activity on free oxygen radicals, tau and beta amyloid protein accumulation, microglial activation, apoptotic cascades, and its most recently defined stimulating effect on brain Aß clearance." In other words, in addition to generating BDNF, it reduces oxidation and inflammation, while booting out beta amyloid and bad tau.  Who could ask for more?

The trials haven't started yet.  We'll see what happens.