Amyotrophic Lateral Sclerosis, aka Lou Gherigs disease. Pretty much sounds like hell, to me. Your mind is fine, while your body is collapsing around you– slowly but surely paralyzing you, taking away your ability to eat and breathe, while your mind is fine and dandy so you are acutely aware of what is happening to you. If youre lucky, youre dead in 3 years. Not so lucky, it can go on for 6 or more. Terrifying.
What makes it even more terrifying, is that the vast, vast majority of people who develop ALS have no family history of it whatsoever. Wikipedia says 95%.
There is *a* drug for ALS. *A*, that might extend someones life for a few months :-/
No cure. And what makes things even harder, no real definitive test.
Well, scientists have made an odd observation– People with sporadic ALS have a shitload of reverse transcriptase activity in their blood. Like, a shitload. Like HIV-1+ numbers.
OMFG ALS IS CAUSED BY A RETROVIRUS SOMEONE CALL THE WPI WARBLEGARBLE!!!
… Um… Nope. Yeah, scientist can reliably find high RT activity, but cant find virus.
Yeah, RT activity all over the place, but no one can find/isolate any actual virus. (Pro-Tip: Its not XMRV) What the hell could cause a phenomenon like that?
I tell you what.
An endogenous retrovirus!
Endogenous retroviruses are what, everyone?
It is good that they are junk. You want them to be junk. One of the many ways our genome has evolved to ensure that these guys are junk is 1) to epigenetically silence ERVs, and 2) let them accumulate mutations.
Thus the vast, vast majority of ‘ERVs’ in your genome are not full ‘ERVs’, that is LTR-gag-pol-env-LTR. Usually they are just solo LTRs. Sometimes everything is mutated except for a gag, or an env, or… a pol:
Despite clinical associations, past approaches to identify a definite causative viral agent in ALS have been unsuccessful. Here, for the first time, we characterized HERV-K polymerase (pol) mRNA and RT protein in brain tissue from patients with ALS and compared it to non-ALS individuals. We show that there is overexpression of select HERVs in patients with ALS and that HERV from these specific cytogenetic loci may be markers of ALS, as well as other motor neuron diseases.
Quick summary– they looked at the brains of people who had died from ALS, people who died from some other chronic condition, people with Parkinsons, and people who just died from accidents. ALS patients had twice the HERV-K pol mRNA expression as the chronic disease group, 10-fold higher than the Parkinsons and accidental deaths.
There are lots of ‘HERV-K’ loci, though. Is one causing all the trouble, or is this a global effect, an increase in transcription of all HERV-Ks? While lots of patients expressed lots of HERV-Ks, only one HERV-K loci was totally unique in the ALS patients, one on the long arm of Chromosome 7. However, only 6 of the 20 ALS patients showed transcription at that particular site, so no silver-bullet there.
Now, something that Larry Moran always reminds us of, when looking at mRNA levels– Our ability to detect itty-bitty-teeny-weeny changes in mRNA transcription does not necessarily mean that there is any damn difference. You have to establish that those differences in mRNA levels actually translates into differences in protein levels. So, the next thing they did was look for RT proteins via immunofluorescence. Antibody to HERV-K RT is linked to a fluorescent protein, ie, the protein ‘lights up’ if its there, the image is dark if its not there. ALS patients brains light up when they look for HERV-K RT.
Okay, then! Wayward HERV-K expression causes ALS then! HUZZAH!
See, another protein is overexpressed in the brains of people with ALS, TDP-43. Cells that have wayward HERV-K RT expression also have wayward TDP-43 expression. Which means we still dont know if HERV-K expression is 1) the cause of ALS, 2) a harmless side-effect of chromosomal disregulation, aka, just a marker for ALS, or 3) a side-effect of global chromosomal disregulation that perpetuates ALS.
I am leaning against #1, because a clinical trial involving an RT inhibitor in ALS patients did nothing. Probably just a side-effect. In any case, this might lead to putative treatments of ALS like with Hodgkins lymphoma, or at the very least, a diagnostic test looking for HERV-K RT.
Very proud of these authors for not overpumping their data, and making it clear that what they have found “may be markers of ALS”:
These findings identify novel HERV-K and genomic markers of ALS, which may have important implications for defining the pathophysiology of sporadic forms of this disease. However, the mechanisms by which these viruses cause or contribute to pathological changes requires further study.
No hype, just letting the data speak for itself. *nod*
Side-note for long-time ERV readers– This post might sound familiar to you. Very familiar. The difference is, HERV-K RT transcripts in ALS patients are found in neurons, while the HERV-W Env proteins are found in glial cells in MS.