An Anti-Alzheimer’s Update

A new gene discovery for Alzheimer’s – the variants carrying the protective and the predisposing genes are only in 1% of us (don’t bother getting tested) – has important implications for this disease that ravages so many in the world, including 6 million in North America (plus their 12 million caregivers). When news broke last week, it reminded me it was time for an update on what we thought was a breakthrough therapy.

Posted on | Mike Roizen, MD | Comments ()
An Anti-Alzheimer’s Update
An Anti-Alzheimer’s Update

A new gene discovery for Alzheimer’s – the variants carrying the protective and the predisposing genes are only in 1% of us (don’t bother getting tested) – has important implications for this disease that ravages so many in the world, including 6 million in North America (plus their 12 million caregivers). When news broke last week, it reminded me it was time for an update on what we thought was a breakthrough therapy.

In February, I wrote about an already FDA-approved drug that might reverse Alzheimer’s. Your brain cells put out waste products or “poop” in the form of beta-amyloid protein. Normally, you have a garbage truck in the form of Apo E that comes along and picks up that poop. If one of the Apo E genes you get is a mutant or dysfunctional, your risk of Alzheimer’s disease goes up about 30%. If you have two, it goes up more than 60%. Lack of function of this gene leads to the human form of Alzheimer’s disease.

When some scientists from Case Western Reserve gave an already FDA-approved drug (it was approved to treat a specific cancer – and it does cause liver, thyroid and blood cell problems in some people, birth defects, kidney failure and some other not-so-pleasant things) to mice bred to develop Alzheimer’s, 25% of beta amyloid disappeared in the first day and 75% of it in 3 days. If you extrapolate that to human studies, that would be the same thing as 75% of that plaque disappearing in 100 human days. But, more importantly, brain cognition returned (in mice it was the ability to have nesting behavior and to sense smells).

So what’s the update?

We cannot find published reports of replication of these reversal findings from other labs. That is disappointing as you might suspect that scientists from all over the world would be trying to replicate any finding this important. The good news: I know of two groups now testing this drug in humans with early and with late Alzheimer’s. We will know within a year if this really stands a chance of being a real breakthrough. Either the mice studies will be confirmed in other mice, or, if we are really lucky, we will have early indications from at least one of the two human studies. I’m praying yes, as this would be a huge, huge advance.

And what’s the new gene data about?

Seems some other scientists – from Iceland and from Roche in Switzerland –found that the key to removing the amyloid protein was to have alpha – and not beta nor gamma – amyloid. When cut in the beta position, this amyloid sticks particularly solidly to your brain cells and causes inflammation and brain destruction if not quickly picked up by a “waste truck.” If cut in the alpha position, the alpha amyloid is much more easily picked up by the waste-removal truck. 

Seems these scientists, led by Dr. Kari Stefansson of privately held deCODE Genetics in Reykjavik, found when they sequenced the genomes of 1,795 Icelanders, about one in 200 have a gene that manufactures an enzyme that cuts amyloid in the alpha position, reducing the risk of Alzheimer’s by 80%. 

Unfortunately, about one in 200 of us have a gene that overproduces an enzyme that selectively cuts the amyloid into beta strands, and thus increases Alzheimer’s risk fourfold. The good news: Maybe a drug or process can be developed to increase the alpha cuts and decrease the beta cuts. 

But that’s a long way off, so lets hope the February breakthrough for Alzheimer’s reversal in mice by Paige Cramer, the lead author on the study at Case Western, works in humans. I’m drinking to that hope right now – but only moderately (never drink to excess – that excess kills brain cells, too).  

Blog written by Mike Roizen, MD
Dr. Roizen is a past chair of a Food and Drug Administration advisory committee and a former editor for 6 medical journals with...