Link made to retrovirus Herv-FC1 for RRMS and SPMS

[milesap]

A link has been made to two retrovirus Herv-fc1 for RRMS and SPMS for PPMS Herv-fc16. I think that this study http://www.biomedcentral.com/1471-2377/13/111/ links all the parts of the puzzle; genes, prehistoric viruses like EBV and the immune system. its hard to refute 350 MS patients and 500 control patients. If the herv-fc1 for RRMS and SPMS and herv-fc16 for PPMS retrovirus is discovered in other studies and the HIV drug trial is effective you have the cause and effect of the disease plus a bonafide treatment.

[frodo]

its hard to refute 350 MS patients and 500 control patients.

When we deal with CCSVI, studies of 500 subjects are routinely refuted

[1eye]

When we deal with CCSVI, studies of 500 subjects are routinely refuted

I don't think there is anything routine about trying to refute the results of a large trial. Whatever might be routinely expected, a piece of research should live of die on its own merits.

[Cece]

It depends on the type of studies. We've seen studies of 1200 MS patients but they're not randomized controlled studies. The pedigree of the university and researchers doing the study seems to matter a great deal too.

If medical research were a sport, it wouldn't be Calvinball, because there are agreed-upon rules that are generally followed. But it's also not a linear progression of a single ball down a single field. I guess it would be like playing soccer with many many different colored balls and different goals, and a lot of the balls are weighted so they don't move easily or they dissipate upon being kicked, and when a goal is finally made, someone else has to repeat it exactly or it doesn't count.

Importantly, recent data suggest that MS is influenced by highly active anti-retroviral treatment (HAART) [42,43]. MS is uncommon among HIV-positive HAART-treated persons (incidence rate ratio = 0.3: 95% confidence interval = 0.04-2.2). Although the group-size is small, and the results are not statistically significant, the effect is fairly strong and in accordance with the expected trend suggesting that antiretroviral medicines can curb MS. If these findings are substantiated, it becomes imperative to investigate in a clinical trial, if HAART can be effective against MS and possibly other autoimmune diseases.

Solid evidence points to an involvement of the endogenous retrovirus HERV-Fc1 in the initiation of MS in Scandinavians. Time will show if the more speculative aspects of this review are borne out.

If this gets proven, then there is a treatment method at hand: antiretroviral medicines. I'd be happy with that.

[1eye]

If the findings are repeated, and all the ducks are in a row for 10 or 15 years of clinical drug trials, what does this mean about 'MS"? CCSVI? People who are not HIV-positive?

I thought Calvinball was played with bases and a bat. If it has the same amount of jargon/lingo/slang etc. as baseball and medicine, it's probably very similar. I suppose the rules, such as they are, have been known to be flaunted at times, by pharmaceutical interests and/or doctors and researchers with conflicting interests, or past affiliations.

[Cece]

Calvinball is a game invented by Calvin in which one makes the rules up as one goes along. Rules cannot be used twice. No Calvinball game is like another. The game may involve wickets, mallets, volleyballs, and additional equipment as well as masks.

http://calvinandhobbes.wikia.com/wiki/Calvinball

A random reference on my part, sorry. Since medical research is not Calvinball, eventually MS and CCSVI will get figured out and the correct treatment will be figured out, whatever that is. This will be very good for the generation in which this happens, and painfully lousy for the generation that just misses. Honestly I think we're close.

[1eye]

Calvinball is a game invented by Calvin in which one makes the rules up as one goes along. Rules cannot be used twice. No Calvinball game is like another. The game may involve wickets, mallets, volleyballs, and additional equipment as well as masks.

http://calvinandhobbes.wikia.com/wiki/Calvinball

A random reference on my part, sorry. Since medical research is not Calvinball, eventually MS and CCSVI will get figured out and the correct treatment will be figured out, whatever that is. This will be very good for the generation in which this happens, and painfully lousy for the generation that just misses. Honestly I think we're close.

Randomocitousness is mainly tolerated in these environs.

The single negative study has broken links. Mysteriously, they all seem to point at the same, wrong paper, which also seems to be open-access.

Nissen KK, Laska MJ, Hansen B, Pedersen FS, Nexø BA: No additional copies of HERV-Fc1 in the germ line of multiple sclerosis patients.

Virol J 2012, 9:1-4. PubMed Abstract | BioMed Central Full Text | PubMed Central Full Text OpenURL

This one:

GNbAC1, a Humanized Monoclonal Antibody Against the Envelope Protein of Multiple Sclerosis—Associated Endogenous Retrovirus: A First-in-Humans Randomized Clinical Study

François Curtin, MDemail address
,
Alois B. Lang, PhD
,
Hervé Perron, PhD
,
Marion Laumonier, MSc
,
Virginie Vidal, MSc
,
Hervé C. Porchet, MD
,
Hans-Peter Hartung, MD

Accepted 12 November 2012. published online 03 December 2012.

Abstract
Full Text
PDF
Images
References

Abstract
Background

Human endogenous retrovirus (HERV) genes represent about 8% of the human genome. A member of the HERV family W, the Multiple Sclerosis–Associated Retrovirus (MSRV) gene, encodes an envelope protein (Env), which can activate a proinflammatory and autoimmune cascade through its interaction with Toll-like receptor 4. Due to its proinflammatory property and an inhibitory effect on oligodendrocyte precursor cell differentiation, the MSRV-Env protein could play a crucial role in the pathogeny of multiple sclerosis. GNbAC1 is a humanized monoclonal antibody of the immunoglobulin G4 type, which is directed against MSRV-Env. After validation of the MSRV-Env as a therapeutic target in preclinical experimental models, a clinical development program was initiated.
Objective

This study evaluated the safety profile, pharmacokinetic parameters, and immunogenicity of GNbAC1 in healthy male volunteers.
Methods

In this first-in-humans, Phase I, randomized, double-blind, placebo-controlled, dose-escalation study, each subject received a single dose of IV GNbAC1 0.0025, 0.025, 0.15, 0.6, 2, or 6 mg/kg or inactive vehicle (placebo), infused over 1 hour. Tolerability and other laboratory parameters were observed, and regular blood sampling was performed, to study the pharmacokinetic properties and immunogenicity of this monoclonal antibody.
Results

A total of 33 male subjects (mean age, 44 years) completed the study. GNbAC1 was well tolerated after dosing in all subjects and in each dose cohort. Only minor and nonspecific adverse events (AEs) were recorded; no serious AEs were reported. Pharmacokinetic data show a dose-linear pharmacokinetic profile. The mean elimination half-life ranged between 19 and 26 days, with therapeutically efficient concentrations maintained over a 4-week periods at doses of 2 and 6 mg/kg. No emergence of anti-GNbAC1 antibodies were detected after dosing in any subject over the entire observation period of 64 days.
Conclusions

In these healthy male subjects, the safety and pharmacokinetic profiles of GNbAC1 appeared favorable. These findings are expected to allow for the launch of a Phase II development program for this innovative therapeutic approach in patients with multiple sclerosis. ClinicalTrials.gov identifier: NCT01699555.

seems interesting, because they are expecting Phase-II. If it's that good, maybe Phase-II and Phase III can be combined. However, efficacy in this case is limited to the reduction of incidence of the MS-associated retrovirus. Whatever affect this may have clinically is not elucidated yet. Seems to me it still could turn into another blind alley.

The prevalence study cited is interesting to me as an anecdote. The prevalence in the Orkney islands seems to be higher even than Northern Ireland. My ancestors came from the Republic, which seems to be lower, but I visited the Orkneys only a few years before my first persistent symptoms appeared. If there is an environmental or pathogen connection to the Orkneys, I may have been exposed to it. My personal opinion is that something about this disease that influences it long-term is a cumulative phenomenon initially. Long-term course of the disease would depend on initial accumulation of some pathogen-exposure or environmental toxin exposure. That would possibly be coincident with exacerbations.

[David1949]

It lends credibility to the hypothesis that PPMS is a different disease.

[1eye]

What is the difference between Herv-fc16 and Herv-fc1? What is the difference between PP"MS" and RR"MS"? PP"MS" and RR"MS"? Progression? How about rate of progression? My friend who never had a remission died at the age of thirty. One big difference between instances of "MS" is how fast progression is. If it's a pathogen or an environmental trigger, either way it's dose-dependent. If it's a genetic susceptibility to one of those things, it's still dose-dependent. If it's a retrovirus the course could easily be dose-dependent too.

These are actuarial distinctions. To the sufferer, the disease has very similar effects, and it doesn't matter. The treatment eventually becomes nil. RR"MS" will eventually likely become SP"MS". I have only had a remission because of the CCSVI procedure in at least ten years. My exacerbations are pretty rare now too. Still progressing in some ways, but slower than before. Many things have not gotten any worse since 1990. But I think the only reason my friend died at 30, and I am still alive at 59, is the rate of progression. Plus what we may be now finding, the prone position could be bad news, and he spent quite a lot of his last years confined to a bed.

[marcstck]

I wrote an extensive post on the subject in wheelchair kamikaze several months ago. There is a trial going on in London using an off-the-shelf anti-HIV drug to treat MS patients. About a week after I put up the post, one of the researchers left a comment on it, and I emailed him to thank him. He requested my phone number, and called me all the way from London! He was very enthusiastic about this research, and Even though the trial is still recruiting, I got the feeling that they may have seen some positive results outside of a trial setting.

It's important to understand that this doesn't involve infections with new retroviruses, but rather the activation of ancient retroviruses that have become part of the human genome during the course of evolution. In fact, 8% of human DNA is made up of ancient viral material that was infectious in the distant past, but has since been incorporated into the human genome. In several hundred thousand years, the same will probably be true of HIV.

Here's a link to the post, which explains the hypothesis, and also talks about the two trials now underway. Importantly, the human endogenous retrovirus hypothesis may come into play not only in MS and/or other autoimmune diseases, but also some cancers and even schizophrenia. Lots of links to relevant abstracts are included:

http://www.wheelchairkamikaze.com/2013/ ... op-ms.html

IMO, this is THE most important research now underway in regards to MS and related diseases. It elegantly ties up almost all of the idiosyncrasies of MS epidemiology, and may finally point us in the right direction in our search for the underlying cause of such illnesses.

[David1949]

Marc
May I ask what type of MS you have? As I read this it sounds like it might hold promise for people with RRMS but not for those of us with PPMS. Is that your understanding?

Dave

[marcstck]

Marc
May I ask what type of MS you have? As I read this it sounds like it might hold promise for people with RRMS but not for those of us with PPMS. Is that your understanding?

Dave

Dave-if I do have MS, it's PPMS. However, my disease is so atypical that there is the distinct possibility that it's not MS at all. Unfortunately, none of the many world-class neurologists and other physicians I've visited has been able to give me a differential diagnosis. So basically, I have a diagnosis of PPMS strictly by default.

Having said that, human endogenous retroviruses have been implicated in not only MS but a host of other autoimmune diseases, cancers, and even schizophrenia. The research paper cited at the beginning of this thread identified an endogenous retroviruses that is implicated in RRMS but not PPMS; however, the same paper identifies another endogenous retroviruses that does seem to be implicated in PPMS. Therefore, antiretroviral therapy should be of use in both flavors of the disease if the hypothesis is correct.

[CureOrBust]

8%? I am sure I have previously heard of a higher percentage.

http://www.bbc.co.uk/news/science-environment-17809503

Astonishingly, only 1.5% of the genetic material in our cells codes for human life. Half of the rest is sometimes described as "junk DNA" with no known function, and the other half consist of genes introduced by viruses and other parasites.

So, if my maths is right, they peg at nearly 49%

http://www.cracked.com/article_19161_th ... r-dna.html

we modern humans have about 100,000 of these microscopic gate-crashers cluttering up our DNA. When you add in the assorted genetic trash they've left behind, more than 40 percent of human DNA is made up of ancient, sinister and almost certainly cursed viruses.

This last link doesn't have a number but came up in my search, and gives some general (ie non ms) background on the topic http://phys.org/news195129587.html

[1eye]

You folks ever feel like you're on the bleeding edge of something you won't live to see?

[MSBOB]

These viruses fit the disease profile well. They attack B cells responsible for the immune system and how the body distinguishes between self and nonself. An infected B cell can repress the body's instructions for the cell to self destruction if it has been miscoded. Basically, if the cell had become sensitized to myelin at the time it was infected, the cell becomes immortalized - and so does the sensitivity to myelin. These viruses have complex life cycles. They explain almost all of the epidemiology and physiology of MS, including epigenetic switches linked to vitamin d, ancestory, age of onset, and many biomarkers that have been studied for decades.

People don't get spinal taps to test for MS. They get spinal taps to test for oligiobands and/or WBCs in the spinal fluid. TI think the only thing known to cause both are viruses (correct me if I am wrong). This is one reason why I believe interferon has has some success. It represses stages of the virus lifecycle. So where does that leave us? My hope is in epigenetics. Companies like Sangamo and Opexa are worth watching.

Best regards