If something sounds too good to be true, it usually is. But sometimes it isn’t. The most exciting exception to this rule of thumb I’ve ever seen is the potential of novel selective HDAC2 and HDAC3 inhibitors to cure neurodegenerative diseases including Alzheimer’s, depression, Parkinson’s, as well as boost the intelligence, memory, and ability to learn of “healthy” neurotypical humans. Other HDAC inhibitors can also cure or at least reduce the symptoms of cancer, diabetes, heart disease, and virtually every other chronic disease.
Don’t Get Your DNA in a Bunch
First, some background. Within every cell in our body, the strands of our DNA are wound up into a ball called chromatin by proteins called histones. Which genes on the DNA are expressed and translated into proteins is determined by how tightly the histones coil the DNA. The more tightly the DNA is coiled by the histones, the fewer genes will be physically exposed to DNA polymerase; those genes that are coiled up and hidden from DNA polymerase will not be expressed and translated into protein.
The Epigenetic Miracle Cure
The family of enzymes that controls how tightly the histones coil DNA is called the histone deacetylases, or HDACs. The more HDACs you have in your cells, the more tightly the DNA will be coiled around the histones and the fewer genes will be expressed. Why might this become a problem? Well, the most obvious example is if an HDAC silences a gene that induces apoptosis (healthy cell death), cell differentiation, or some other important gene controlling the cell cycle, which gives you cancer. And indeed, HDAC inhibitors that shrink tumors have been on the market for years now, most prominently for hematological cancers like refractory T-cell lymphoma.1 2 3
More recently, scientists have been discovering that inhibiting the various HDACs can do a lot more than just shrink cancer tumors. According to one study, “HDACs are implicated as a regulator in various pathological heart diseases such as fibrosis, arrhythmia, ischemic heart diseases, and heart failure.”4 According to another,“Surprisingly, HDAC inhibitors have also been shown to be efficacious in preclinical models of heart failure.”5
Just in case you weren’t already convinced that HDAC inhibitors are the most awesome thing since the invention of antibiotics, it gets even better. HDAC inhibitors have also proven effective at treating neurodegenerative diseases like Alzheimer’s, dementia, Parkinson’s, Huntington’s, and depression.10
So what’s the catch? Why isn’t there already an HDAC inhibitor panacea drug for all that ails you on the market? Well, the problem is that there are at least eighteen different kinds of HDACs, which are grouped into four different classes. Some HDACs do good things, and only a small minority of them seems to be responsible for disease.11
The good news is that we now know which ones are the bad guys and which are the good. HDAC3 appears to cause over seventeen inherited neurodegenerative diseases, including Huntington’s.12 HDAC6 is implicated in the pathogenesis of Alzheimer’s, Parkinson’s, ALS, FTLD, and CMT.13 HDAC2 is the principal villain behind diabetes, inflammation, depression, Alzheimer’s, and dementia.14 15 16 17 18 Perhaps most excitingly, not only does inhibiting HDAC2 and HDAC3 reverse these diseases, it also has the potential in healthy humans to enhance neuroplasticity and improve the ability to remember, form new memories, and learn, making it the ultimate nootropic or “smart-drug”.19
Unfortunately, the only HDAC inhibitors on the market today are woefully non-specific, meaning that they inhibit several kinds of HDACs, the good and the bad. That doesn’t mean specific inhibitors of HDAC2 and HDAC3 don’t exist though. It just means they’re stuck in the research phase.20 However, a patent entitled “INHIBITION OF HDAC2 TO PROMOTE MEMORY” detailing exactly how to make your very own HDAC2 inhibitor is freely available online here. I’ve got a 93 year old uncle with dementia who’s quality of life and happiness would be greatly increased by taking an HDAC2 inhibitor to whom I’d like to offer the option, so if you are or know a chemist capable of synthesizing this compound, please let me know.
Over the Counter HDAC Inhibitors
Worth mentioning is that curcumin, the active compound found in the spice turmeric, has been found to reduce inflammation, prevent stress induced damage to various organs, inhibit tumor growth in cancer, reduce depression and seizures, and improve memory and learning. 21 22 23 24 25 26 27 28 29 It is a non-specific HDAC inhibitor that is easily and reasonably cheaply available over the counter. It’s probably not as effective as future specific HDAC2 and 3 inhibitors, but it won’t hurt you either—in fact it will probably help significantly with a variety of diseases—and it’s the easiest to get next best thing for now.