Neurological Correlates

Let’s say the day comes when you are told you have pre-Alzheimers. You are told that getting the disease is inevitable. Emotionally, you grieve for your own “lost” personality. Your loved ones prepare for your care taking — or to put you in assisted living at an outrageous expense to someone.

Then this report hits like a bombshell: A shot of a known, safe drug to the spinal fluid could save your mental-health life. The drug has been on the market for some time — used to treat rheumatoid arthritis, among other things. The side effects are known, but they mostly relate to over- suppression of the immune system.

You pack your credit cards, cash and checkbook and rush out to the doctor’s office, clamoring to try the treatment, anything to avoid Alzheimer’s.

“Doctor, please” you say, “I don’t want to lose my lifetime memories!”

But the doctor says, “No, this wasn’t a full clinical trial, so the data may not be for real. Plus, it goes against almost everything we know about Alzheimer’s. And, it doesn’t make any sense that it works, so I don’t believe the published reports, they must be just wishful thinking. It’s only 15 patients! That proves nothing. No, you don’t get this drug. Go back to eating fish oil.”

So what’s this all about?

Spinal injection of a known anti-rheumatoid arthritis medication immediately reduces the symptoms of Alzheimer’s in humans. From “Commentary, Perispinal etanercept: Potential as an Alzheimer therapeutic,” by W. Sue T. Griffin, Journal of Neuroinflammation 2008, 5:3doi:10.1186/1742-2094-5-3

Toward such manipulation in Alzheimer’s disease, a six-month study was conducted with 15 probable-Alzheimer patients who were treated weekly with perispinal injection of Etanercept, an FDA-approved TNF inhibitor that is now widely used for treatment of rheumatoid arthritis and other systemic diseases associated with inflammation. The results demonstrated that perispinal administration of etanercept could provide sustained improvement in cognitive function for Alzheimer patients. Additionally, the authors were impressed by the striking rapidity with which these improvements occurred in the study patients. An example of this rapid improvement is presented in this issue as a case report by Tobinick and Gross. Such rapid gain of function inspires speculation about the role of gliotransmission or other equally rapid synaptic events in the relationship of TNF to Alzheimer-impacted neurophysiology.

Here’s a link to a case study with an individual patient, Edward L. Tobinick, Hyman Gross, “Rapid cognitive improvement in Alzheimer’s disease following perispinal of etanercept administration,” Journal of Neuroinflammation 2008, 5:2 (9 January 2008). About 2 hours after receiving Enbrel, the Alzheimer’s patient tested much better on clinical tests for Alzheimers.

This is amazing to me for two reasons:

1. This is a new way to think about Alzheimer’s — as your body launching the inflammation battalions against your brain. Before, it was thought that particular, insoluble little dabs of gunk somehow intractably formed in your brain, and the key was to prevent them from forming or to flush out the gunk that already formed.

As the commentator noted, this is a change in direction against the Alzheimer’s research community.

The Alzheimer’s research “establishment” is going to be up in arms about this one. If this is the “cure” or at least a pretty effective treatment — and the mode of action is known, the delivery is known, it’s an already approved drug, it’s being made and quality-controlled tested in approved factories — then that pretty much sidetracks the other researches, imo.

This reminds me of the guys who figured out that a bacteria causes ulcers — no one believed them for a long time, and then they won the Nobel Prize.

2. A protein — here, etanercept (branded Enbrel(r)) gets past the barrier in the brain that is the “gatekeeper” to what moleules can enter the brain — the blood brain barrier. Unlike what you were taught about LSD in high school — that if you take it once, it will always be in your brain and you’ll have flashbacks when you’re 30 — most things don’t get in the brain, and if they do, they don’t do any good , especially not big molecules like proteins, and you don’t have flashbacks. So from a protein pharmacokinetic point of view, this is really interesting.

This is very new. I think it is pretty powerful, but let’s see.