I’ve never been devout. I was raised in a secular Jewish home. For my parents being Jewish meant a connection to a people, not to any creed or book. I owe my life to that distinction.
Most of my great grandparents were devoutly religious. When the Nazis occupied Poland in 1939 their children, my grandparents, saw the writing on the wall and went East where many fought for the Russian Red Army. They urged their parents to come with them but most refused believing god would save them.
None who stayed survived the war.
So, you may understand why I might be predisposed to be opposed to any kind of faith-based teaching. However, I now find myself having to rely on faith. So much so that I just had two holes drilled through my brain.
Deep Brain Stimulation has been an approved therapy for 24 years and has been performed over 160,000 times, yet, we don’t know how it works. There are theories that it either blocks neuronal output or indirectly inhibits certain axon terminals or resets misfiring neuronal activity, but none have been proven. DBS was discovered using the same time-tested method as much of medicine, guess and check.
I was asked recently in an interview “what is it like to go through a procedure for which we don’t know how it works we only know that it works?” Well, that’s the thing about being a patient, you have to have faith. Faith that your doctors know what they are doing and have your best interest at heart, faith that this procedure which has worked on thousands of patients in the past will work on you, and faith that the system that regulates the practice of medicine is working to keep you safe.
You might say that this is a false equivalency, that medical science is independently verifiable and is based on reason, facts and objective truth. A few years ago I may have agreed with you, but if I have learned anything in my journey it is that medicine, especially that which drives neurodegenerative research, is based on systems of belief. Sometimes it performs miracles, sometimes it can lead us astray.
The figure above comes from a manuscript just released today titled High cerebrospinal amyloid-β 42 is associated with normal cognition in individuals with brain amyloidosis. What it shows is newly analyzed data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI), the largest database of its kind. In it researchers found that higher levels of amyloid plaques, believed to be the hallmark of Alzheimer’s disease, do not correlate with cognition. Similar amounts of plaques were found in both healthy controls and people diagnosed with Alzheimer’s. What differentiated the two groups was not how much plaques they had, but how much soluble Aβ42 peptide was in their cerebral spinal fluid. The healthy group had much higher levels.
This finding flies in the face of everything most neurodegenerative researchers have been telling us about the brain. In fact, a drug was just approved on the basis that it will do the opposite of what this paper reports. If this new report is correct, that drug will accelerate cognitive decline in patients who take it, as happened in many previous trials targeting Aβ amyloids, shown in the table below courtesy of my co-author of Brain Fables, Prof. Alberto Espay.
The global standard bearer that regulates medical science has been the United States Food and Drug Administration (FDA). Since they reformed following the thalidomide scandal of the early 1960’s, the FDA has proven themselves to be the world’s leading authority in regulating medical science. Regulatory authorities around the world often take their cues from the FDA. This was exemplified most recently with the remarkably successful development and distribution of vaccines against Covid-19.
However, their reputation is now being questioned. Three weeks ago the FDA chose to grant authorization to Biogen for their Alzheimer’s drug aducamunab, the drug mentioned above, on the basis that it will reduce amyloid. They did this because they believe amyloid build up causes of cognitive decline. I use the word belief because the available evidence isn’t clear, their own advisory committee recommended to deny approval, three of whom have since resigned.
There is a lot more I could say about that decision but most of it has already been told far better than I could in this this brilliantly scathing critique from the usually neutral Science of Parkinson’s. Highly recommend reading it before continuing on below.
In late August 2019 I took a trip to Copenhagen to visit the pharmaceutical company, Lundbeck. I had last been in Denmark when I was two years old, my parents lived there for a couple months before immigrating to Canada. We originally went to see my Mom’s dying Father, who had fled to Denmark when Jews were again pushed out of Poland in the late 1960’s.
I have no memories of my maternal grandparents but while preparing for the trip I noticed that their cemetery was within walking distance of my hotel. So, determined to make at least one memory of them, I took a walk through the idyllic streets of Copenhagen to the cemetery pictured above. The only clue I had to guide me upon arrival was a half obscured picture of their grave my Uncle had given me.
I soon felt as if he was testing me. The cemetery was a maze of tombstones. There were thousands of plots in scattered rows of every shape and size you could think of. I checked nearly every grave in that cemetery for three hours until I found it in the second to last row I had left.
While in Copenhagen I shot this video. It is hard for me to watch to be honest, always a little difficult to see the patient side of my advocacy. But I think the message is on point and am grateful to the team at Lundbeck for putting it together.
In that video you can see a glimpse of a presentation I would deliver to many other biotech companies about how I saw the field and what I think needed to be done to push things forward. One of the topics I touched on was protein aggregation, whether my words were headed I’m not sure, but there is one more argument I wish I had made.
There is one question underlying much of drug development in neurodegenerative diseases, is protein aggregation toxic? Either it is and we need to figure out how to break up the aggregates and stop it from clumping together, or it is a harmless byproduct, or it could be protective and we actually need to replace what is lost. My intuition is that it is some combination of all of the above and your answer is determined by when and where you choose to look. Aggregation is a complex process, at certain stages and under certain conditions it may appear toxic, at others it may seem harmless, and at others still it might confer some benefit.
But, even if it is primarily toxic, the next question would then be, do we understand this phenomenon well enough to make a drug that can effectively target it. Some experts say we do, some say we don’t. As a non specialist it’s nearly impossible to know what is right. After reading reviews such as this one published last week from one of the foremost experts on the subject, Prof. Hilal Lashuel, I can’t help but think that the science just isn’t there yet for us to be able to confidently say we know how to intervene.
“In spite of decades of research on the mechanisms of amyloid formation and the structural properties and mechanisms of toxicity of the various types of aggregates that form along the amyloid pathway, many fundamental questions about the role of this process in the pathogenesis of NDDs remain unanswered.”Prof. Hilal Lashuel
To be honest, I don’t know what to believe but suffice it to say the science is far from settled and I am concerned for the well being of any patient that takes this drug.
This decision by the FDA will likely trigger a rush for various companies to seek approval for drugs on similar grounds. Meaning we may soon see drugs approved that claim to slow the progression of ALS, Huntington’s, Parkinson’s and more based on surrogate biomarkers, not the disease itself. Thankfully, there are some powerful groups that also see an issue here; Congressional Democrats launch probe into Biogen’s Aduhelm FDA approval, citing ‘serious concerns‘.
This decision has shaken my faith in the FDA, and by extension, the process that governs medical science. I no longer trust that they have my safety and best interest at heart.
So, where do we go from here? What happens after faith in a system has been shaken? Well, either the system finds a way to rectify itself, or people put their faith in something else. That’s the thing about faith, it is fickle. The problem is, witchdoctors have never had it easier. At no other time has it been so easy to deceive so many. We need people to have faith in institutions like the FDA more than ever.
But there’s still hope, the FDA can and should reverse their decision. Which is why I am joining voices like Public Citizen in Calling for the Resignations of Acting FDA Commissioner, (and) Other Top Officials Responsible for Indefensible Approval of the Alzheimer’s Disease Drug Aducanumab.