For those of you that follow the latest research on postural orthostatic tachycardia syndrome (POTS) regularly, this is probably old news. But for those of you that don’t…
A recent study out of an Australian university has discovered the genetic suppression responsible for POTS. For a while now, researchers have known that something with the norepinephrine (aka noradrenaline) transporter (NET) gene (SLC6A2, found on chromosome 16) goes wrong in POTS patients. Apparently, a repressor protein called MeCP2 and a non-coding RNA (let-7i) together cause the suppression of the NET gene.
I’m going to be honest, I have no idea what that means. I’m no scientist, or English major, or even a person who is good with word-whatzadingles. I’ll do my best to break it down, so we can figure it out together.
You see, MeCP2 is a beloved unit protocol drone built by Anakin Skywalker on Tatooine.
Just kidding. Star Wars joke.
MeCP2 is a protein-thingy that helps normal nerve function. Non-coding RNAs can cause structural changes to chromatin (part of a chromosome). The MeCP2 interacts with the RNA hoozywhat to induce changes to the NET gene, which silences normal gene function, meaning the gene doesn’t make enough NET protein.
The NET gene is responsible for the reuptake of norepinephrine. Norepinephrine, also known as noradrenaline, is increased during stages of stress or danger – the fight or flight stage. When the MeCP2 and let7i silence the NET gene, it results in decreased NET activity, which I understand may be responsible for the norepinephrine spillover to plasma in POTS patients. [Norepinephrine spillover means higher-than-normal levels of plasma norepinephrine.] That shit just overflows, like champagne bottles. Or lava. Lava is better.
So, short story even shorter, this protein combo causes the NET gene to malfunction. It’s like if Darth Vader and Emperor Palpatine got together to build the Death Star, and the Death Star silenced the rebellion. Cool, right?
[Whew. I had to spend like 5 hours and read 13 different journal articles to give you those two paragraphs. Scientific-ing is hard.]
But that’s not the big news. Hold on to your pants.
Researchers believe they may have found a treatment that would reverse the silencing of the NET gene. Meaning we may have found the plans for the Death Star.
White blood cells from POTS patients were treated with a drug called Vorinostat, which, yes, sounds like the name of a Lord of the Rings or Game of Thrones character, but is in fact a drug used to treat lymphoma. It’s a chemotherapy. In those POTS white blood cells treated with Vorinostat, NET protein levels increased. Which means Vorinostat may reactive the NET gene. Which means normal gene function would be restored. Which means, if the NET gene is silenced in POTS patients, reactivation could result in a decrease or elimination of POTS symptoms.
Which means Vorinostat could potentially cure POTS in some patients.
Before you go out and blow your life savings on stock in Merck (the maker of Vorinostat), be sure to read the fine print. The study was only conducted on 9 patients, so the data is limited. And, I haven’t heard any speculation about how those who have POTS secondary to some other illness (e.g. EDS, MCAD, lyme, etc) will respond. While the research is promising, this may not be the cure we are looking for.
But friends, we’ll get there. The journey of a thousand miles just began with a single, dizzy step. Put on your Fitbits- we’re going for a long walk.
Or, to continue my Star Wars analogy, we have the Death Star plans, but it will take a while before we actually destroy it. We’re somewhere between Rogue One and Episode IV. Or maybe early into Episode IV, but after Princess Leia has been captured, because clearly I’m Princess Leia in this fantasy, and I have been silenced by the “Death Star” (POTS). But don’t worry, me and the hot smuggler are totally going to make out in the end.
Sorry…what were we talking about?
“What is now proved, was once only imagined.” – William Blake
Smell ya later.