protect your brain!
Drugs v. Diet in Alzheimer's Prevention - and This Week's Zoom!
Just the other day, the following story appeared in the news: the FDA declined to grant accelerated approval to Eli Lilly pharmaceuticals for an experimental Alzheimer’s drug called Donanemab that they’re looking to speed to market. It’s really not such an earth-shattering story, on its surface. After all, the company expects to be able to file full clinical trial data later this year, at which point, presumably, the drug will be approved.
But there’s always a story beneath the story — or in this case, two stories — and that’s where it gets interesting.
first, the bad news
A year or so ago, the FDA issued accelerated approval for another Alzheimer’s drug, Aduhelm, made by biotech firm Biogen. Great. A drug that can help the 6 million Americans living with this terrible disease is a good thing. But it turns out the FDA didn’t exactly dot all its i’s and cross its t’s, and the whole thing gave rise to an 18-month congressional investigation.
Just last month, the result of that investigation was issued in a report. It found that there was “atypical collaboration” between the FDA and company representatives, and the agency “sidestepped expert outside advisers who said clinical trials failed to prove effectiveness of the drug.”
Oh, and the cost to patients is fifty-six THOUSAND dollars per year. (Apparently, Biogen was hoping for a “blockbuster” that would “establish Aduhelm as one of the top pharmaceutical launches of all time.” Eat your heart out, James Cameron.)
Oops.
then, the other bad news
So it’s understandable that the FDA might want to slow its roll a bit on the accelerated-drug-approval front, if only to save face. But here’s where things get even weirder.
Adulheim, Lilly’s new Donanemab, and several other new Alzheimer’s drugs work by targeting and removing amyloid plaques, sticky deposits of protein that — the theory goes — accumulate in the brain and kind of gum up the works, leading to cognitive impairment and eventually, Alzheimer’s. These drugs are the result of decades of time and billions of dollars’ worth of research. According to Science magazine, “NIH spent about $1.6 billion on projects that mention amyloids in this fiscal year, about half its overall Alzheimer’s funding.”
So big pharma, the U.S. Government — all have gone all-in on amyloid plaque. But what if we’ve all been barking up the wrong tree?
here’s where it gets… well, sticky.
Plaques have been suspected of having a causal role in Alzheimer’s disease, ever since Alois Alzheimer himself saw them in the brain of a deceased dementia patient in 1906. However, years of research had failed to confirm this theory.
Then, in 2006, a paper by a freshly-minted PhD researcher named Sylvain Lesné appeared in the journal Nature magazine. It announced the discovery of a specific substance called Aβ*56 (amyloid beta star fifty-six), and showed pretty definitively that this was the substance that was causing all the trouble.
We might call it the paper that launched a thousand clinical trials. Science says, “The Nature paper has been cited in about 2300 scholarly articles—more than all but four other Alzheimer’s basic research reports published since 2006, according to the Web of Science database.”
a bit of sleuthing and a bit of scandal…
Last summer, the journal Science published an article called “Blots on a Field?” The subtitle tells you all you need to know: “A neuroscience image sleuth finds signs of fabrication in scores of Alzheimer’s articles, threatening a reigning theory of the disease.”
It’s a long story, but here are some of the beats: an unsuccessful drug called Simufilam, a neuroscientist from Vanderbilt University named Matthew Schrag, and a six-month follow-up by Science uncovered a number of “suspect images in dozens of papers involving Alzheimer’s disease,” going all the way back to Lesne’s original 2006 study.
“The authors ‘appeared to have composed figures by piecing together parts of photos from different experiments,’ says Elisabeth Bik, a molecular biologist and well-known forensic image consultant. ‘The obtained experimental results might not have been the desired results, and that data might have been changed to … better fit a hypothesis.’”
The scandal didn’t exactly make front page news, but organic chemist Derek Lowe, PhD, in an opinion piece published one week later, put it this bluntly: “Every single one of these [amyloid-targeting] interventions has failed in the clinic. Every last damn one. If you look for the best outcome of all, actual reversal of Alzheimer’s symptoms, you never see it.” He goes on to advise, “We have to put money and effort down on other hypotheses and stop hammering, hammering, hammering on beta-amyloid so much. It isn’t working.”
Now we have another round of drugs, based on that same theory, targeting that same target. And it might just work this time around. But maybe it’s also worth asking…
what about those other hypotheses?
And here’s where we get back to our book club pick of the month, Dr. Mary Newport’s Clearly Keto. Because there’s another thing that happens in the brain of a person with Alzheimer’s: what might be called a fuel shortage.
Building on the work of researchers like Dr. Stephen Cunnane and others, Newport points to the fact that the brain in a person with cognitive decline loses its ability to burn glucose for fuel. “Many studies using glucose PET imaging have demonstrated that the problem of getting glucose into brain cells begins at least two decades before symptoms of Alzheimer’s appear,” and gets worse as symptoms deteriorate.
The issues around glucose metabolism and insulin resistance have led some to call Alzheimer’s “Type 3 Diabetes,” or “Diabetes of the Brain.” And just as a ketogenic diet can help people with Types 1 and 2 diabetes to regulate their insulin levels by burning an alternative fuel (fat), it can help help people with Alzheimer’s. That’s because, even as the brain’s ability to burn glucose for energy declines, it remains able to burn ketones, substances that are produced in the burning of fat.
Throughout the book, Dr. Newport relays stories of people who have used ketones to help slow the progression of cognitive impairment, or prevent it in the first place. She also lays out a step-by-step plan for using what she calls a “Mediterranean-Style Diet” with the addition of ketogenic strategies to protect your brain from the insulin resistance and inflammation that are hallmarks of this most dreaded disease.
The book goes on to review a number of other lifestyle choices that can help protect the brain — things like exercise, sleep, stress, as well as particular supplements that help lead to healthy aging. After reading it, you’ll have a solid plan to fight the disease that was once thought to be the inevitable fate of people with bad genes — talk about empowered health!
I’m excited to get on Zoom this week to talk to Dr. Newport about all of it, and I hope you’ll join. Mark your calendars for this Wednesday, January 25, at 6:30 PM Eastern. I’m sure it will be a fascinating discussion, and you’ll have a chance to ask your questions to Dr. Mary directly!
Keep an eye on your inbox: I’ll send the zoom link and all the login details on Wednesday. See you soon!