Incredible Discoveries in Alzheimer’s Research
By Dr. Chris Wheeler, CSO – TNeuroPharma
Something amazing just happened in Alzheimer’s research, and the implications go well beyond the actual data generated.
You see, there are 2 major forms of Alzheimer’s. One is hereditary early onset Alzheimer’s (EOAD). If you inherited a rare mutation in any of three separate genes, you’re guaranteed to get EOAD at a fairly young age. EOAD only represents 5% of all Alzheimer’s cases. The other is age-dependent late onset Alzheimer’s (LOAD) that has no known cause except for aging itself.
The gene mutations that guarantee EOAD all cause sticky protein pieces to build up in the brain – a feature of both forms of Alzheimer’s. These sticky pieces are called beta-amyloid (Ab for short).
Drugs that aim to reduce the build-up of Ab in the brain have been tested as treatments for Alzheimer’s for decades. But more than 96% of them fail to improve the mental decline and memory loss so characteristic of the disease, and some even make it worse. The single drug that looks like it just might reduce mental decline and memory loss in Alzheimer’s – just revealed this past November, 2019 – only slowed their decline, and not by that much. It’s also controversial, because it was initially declared a failure to the FDA, until new data was found by the company developing it. So, basically, attacking the only known “cause” of any form of Alzheimer’s has not really been the most promising way approach to treating the disease.
So – understandably – there’s been a growing sense that we in the Alzheimer’s research and treatment community are missing something fundamental about what causes it and drives its progression. Growing numbers of researchers and physicians are wondering whether Ab build up isn’t the whole story. Others are resolute about Ab being the sole cause of at least EOAD, because it’s otherwise hard to explain how every single person with one of those “causative” gene mutations develops the disease.
This is where the amazing thing I mentioned comes in. Basically, a single person who carried one of those gene mutations that guarantees Alzheimer’s dementia by their 40s, didn’t develop dementia for at least 30 years later in their 70s. If any drug delayed Alzheimer’s that long, it’d be deemed wildly successful; worthy of a Nobel prize or two. So, what was it about this person that protected them from the influence of that EOAD-causing mutation? They had impressive Ab build up in their brain, so it wasn’t anything related to that. With a closer look, though, it was found that they had another even rarer mutation in a second gene that doesn’t directly promote Ab build up.
Without getting into what this gene does and how its mutation might protect against Alzheimer’s, what this means is that EOAD-causing mutations only guarantee EOAD if some other requirement is also met; a requirement that always is met, unless a super-rare event like a second gene mutation compromises it.
This has a couple larger implications: First, EOAD is a disease that requires more than just Ab build up in brain, even if mutations in genes that promote Ab build in brain up guarantee it 99.99% of the time. Second, it aligns EOAD more closely with LOAD, as the Ab-reducing drug failures were all in LOAD. In fact, this dynamic had prompted some to speculate that maybe just EOAD was caused by Ab build up alone, while LOAD had more complicated causes. This single person reveals that the cause of EOAD is perhaps similarly complicated.
This also this puts the Alzheimer’s drug failures into context: We’ve pretty much just been testing drugs that decrease Ab build up in the brain. If something else is required, then we’re aiming at a piece of the problem at best. Knowing there is something else – at least in EOAD – may allow us to determine what drives Alzheimer’s more completely, and that could drastically change how we treat and even diagnose the disease.
We just need to know what that other thing is. At T-Neuro Pharma we think we do, and with that knowledge, we are working to improve diagnosis and treatment for all forms of Alzheimer’s.