Here's how I would do it. First I would talk to a doctor who knows my situation, knows that I am very symptomatic, and show him/her the pilot study where three out of three patients had a significant (but transient) symptom improvement.
If that doesn't help, and I'd still like to give it a go, then I'd look outside the boarders. Personally I just might do that. If someone lives in the US, it might be mexico which is best, if someone lives in Europe, the eastern countries would probably be where it's possible to give it a go.
Nothing is proven to work. But hey we know that. It's a risk benefit thing where we have to weigh them both and decide which one weighs heavier than the other. If I got the chance to try, I would try, without doubt.
- It's not known what the cause of NH Lymphoma is, but it may be XMRV.
- Non-Hodgkin's Lymphoma improves (or gets cured) by using the B-cell depleting drug Rituximab.
- XMRV has been found in B-cells. And may very well depend on B-cells to exist.
- XMRV has been found in CFS patients.
- CFS patients also get a whole lot better when they get a Rituximab treatment (transient, but marked improvement in all symptoms)
Could it be that what happens when people are treated with Rituximab, is that it "hits" the XMRV?
What do you people think?
About XMRV and cancer (NHL):
After all, another retrovirus in the small family of retroviruses known to cause illness in humans can cause both neurological symptoms, but also cancer. I think the same is true for XMRV.
I just browsed through Rituxan.com, and I see that Rituximab also works for Mantle Cell Lymphoma, one of the lymphomas which is in the table above (see the places where it says MCL in the right column).
IL-8 seems to play a central role (significance is rated high in the snyderman paper) in CFS, and it's often elevated to begin with (see graph).
As I read it, elevated IL-8 indicates that RNase L and cytomegalovirus (CMV) are activated.
I don't know how the IL-8 levels are to begin with for RA patients. But they rise with treatment, despite clinical improvement. Strange...
Cytokines and chemokines are key regulatory molecules involved in rheumatoid arthritis (RA). B-cell depletion therapy improves RA clinically but its mechanism is not completely understood. One possible mechanism for this therapy is the modification of the proinflammatory cytokine homeostasis of RA. We show here that the levels of the proinflammatory chemokine IL-8 in serum samples from RA patients unexpectedly increased by up to 100-fold 8 weeks after the administration of rituximab, despite clinical improvement. We also show that RA patients produced anti-IL-8 autoantibodies and that their levels dropped after Rituximab treatment. Moreover, we identified antibody-IL-8 immune complexes in the synovial fluid and serum of RA patients, and found that the amount of these complexes decreased after the administration of Rituximab. Our results indicate that B-cell depletion therapy modifies the cytokine-autoantibody network by reducing the levels of anti-cytokine autoantibodies and, consequentially, the formation of antibody-cytokine immune complexes.
Monoclonal antibodies are the largest class of biotherapeutic drugs. When administered to infected organisms to blunt the propagation of pathogenic viruses, they may also induce a long-lasting and protective antiviral immune response similar to that achieved by vaccination. [...]
Antibodies (AB) are molecules that are produced by the immune system to defend itself against cancer cells and infective agents. Of these, monoclonal antibodies can be developed and produced at a large scale to treat a variety of diseases: cancer, inflammatory or infectious diseases, etc. They thus constitute the largest class of biotherapeutic drugs to date and are being considered with increasing interest for the treatment of severe and chronic viral infections such as HIV (Human Immunodeficiency Virus) or HCV (Hepatitis C Virus), against which current therapies are still insufficient.
Until now, the only mechanism of action of antiviral monoclonal antibodies that was really considered by the medical and scientific communities was the neutralization and direct elimination of viruses in infected organisms. [...]
Click the link. Read the whole text. Lots of interesting info (I found the link in another thread here posted by Hip).
Check out the video if you'd like some more insight into how the monoclonal antibodies work in our bodies.
The [monoclonal] antibodies can bind to the surface of the virus. It can stop the virus' life cycle. And the virus is degraded...
TSG101 is an example of a surface protein which monoclonal antibodies can bind to. TSG101 is, according to Cassella et al vital to all retroviruses tested. Based on the knowledge of TSG101 she proposes that monoclonal antibody treatment could become an effective XMRV treatment.
Monoclonal antibodies are just as different [from each other] as various normal antibodies are different from each other. Some monoclonal antibodies are designed to attach to the surface of viruses, some to bacteria and some to B cells, T cells or other cells.
The text is full of useful info. But I didn't know how much I could quote, so I had to cut out some parts. Anyway, it's worth a read :Retro smile:
And monoclonal antibodies can also work wonders in the disease with many similarities with CFS; multiple sclerosis. A new study suggests that they could get a effect much closer to what you are describing:
"The study, led by researchers from the University of Cambridge, has found that alemtuzumab not only stops MS from advancing in patients with early stage active relapsing-remitting multiple sclerosis (RRMS) but may also restore lost function caused by the disease."
This is their regimen:
[Alemtuzumab] administered through IV, once a day for 5 consecutive days at Month 0
[Alemtuzumab] administered through IV, once a day for 3 consecutive days at Month 12
As we know, those with CFS normally have a pretty messed up proinflammatory cytokine/chemokine levels:
See graph (a little over a hundred patients and healthy controls are tested)
Quote from the Rituximab study:
Among the most consistent immunological abnormalities detected in CFS patients are T- and NK-cell dysfunctions, and decreased intracellular perforin. The B- and T-cell functions are mutually related. B-cells produce proinflammatory cytokines, they are regulators of other effector cells in the immune system, and are efficient antigen-presenting cells.
So, B-cells produce proinflammatory cytokines. I didn't know that.
Most of us have elevated levels of proinflammatory cytokines.
It might be, and I say might, that Rituximab doesn't go to the root of the problem. It only addresses the immune imbalance. So when someone gets a dose, the cytokine/chemokine profile normalizes, one feel better for a while. And when the B-cells are on the rise again, they begin [over] producing proinflammatory cytokine/chemokines...
As we can see in the study above (done on RA), the proinflammatory cytokine/chemokine levels rise to begin with (measured at 8 weeks), but we don't know how it goes later on. Perhaps down. Perhaps not.
Is there anything going on in the US with Rituximab? Because the trials I saw looked like they were only taking place in Norway. Does anyone know, if this being studied by any of the ME/CFS docs in the US?
If it's being studied in the US? Not offical trials. But I'd say "yes" if you asked me if it was being used. But that's unofficial use.
But to fully answer that question. I would like to speak a bit broadly about it (many phrases borrowed from Matthews) ...
During the late 1990s, two medical researchers at University College London began to wonder if B-cell therapy might hold the key to the debilitating disease rheumatoid arthritis (RA).
But there was massive opposition to these new ideas (as it always is when someone tries to change the status quo). They thought that B-cell therapy (Rituximab) could be more useful then existing therapies. The new theory was that B-cell therapy might be useful, or that B-cells had a central role in RA was refused. Their academic papers were rejected by journals as "obviously" wrong.
After much back and forth the pair managed to publish their idea in a medical journal, only to be met with deafening silence. Determined to make their case, they set up a small but demanding test, using rituximab to treat five patients with severe RA. The results were impressive; their condition improved dramatically. Yet attempts to publish the results in journals were rebuffed on the grounds that the study involved too few patients.
So the pair tried again, cobbling together enough money to treat 20 patients. Again, the results were impressive, with all but two of the patients showing dramatic improvements. It made no difference: the medical community remained utterly unimpressed. A long story short, in 2006 the medicine was approved for RA...
What we can learn from that is two things; lack of attention doesn't have to mean it's not right. And it takes (almost always) an eternitiy from idea, to small trial, to being able to get the medicine as a patient.
The primary study endpoint was the total number of gadolinium-enhancing T1 MRI lesions seen at weeks 12, 16, 20 and 24.
The authors found that the total numbers of lesions was significantly reduced in rituximab-treated patients compared with placebo-treated patients at each of the study time points. The mean number of lesions at week 24 in the active treatment group was reduced by 91 percent to 0.5, compared with 5.5 for controls.
As for understandable reasons Rituximab is - by some - being used off label for MS today. But I guess most patients are told to not be so very open about it. In the same way as I am sure Rituximab is being used for MS, I am sure there are some doctors who offer Rituximab for some of their CFS patients. It's a large country, so although non common, I'd say for sure that there are some out there who do it.