"As I've mentioned in previous posts, I am a Tysabri trial patient, and have been on the drug for 3 years. Today I attended a meeting called by my neurologist to inform all the trial patients about what's been going on. I'll update you with a few key points.
First of all, the two patients were in Colorado and San Francisco. The first patient started showing symptoms in December - paralysis on one side and severe cognitive impairment such as difficulty speaking. She was given steroids, but this was only after she presented the symptoms so really the steroids had nothing to do with her getting PML. She was given another dose of the Tysabri and another round of steroids before they figured out that it was PML. She passed away shortly afterwards. An autopsy confirmed diagnosis of PML.
The second patient is male and in San Fran. He started showing similar symptoms soon after the first patient but his Tysabri was stopped right away so he is paralyzed and still in hospital but for the moment stable.
Both patients were on combo (Tysabri+Avonex) therapy. No evidence of any PML has been found in anyone in monotherapy. It is thought that the combination of drugs is just too much for the immune system. As you may know, PML is caused by sudden activation of the JC Virus - a virus which is present in 80% of the population. It just usually lays dormant - controlled by the immune system. The combination of drugs perhaps suppresses the immune system too much, and allows the virus to re-activate. If the drug is brought back on the market, it will likely be stand-alone. When it will be brought back will depend on whether they find any other suspicious cases. "
If they are calling in the patients on a Sunday to update them, then this could be BIG NEWS, right? First they would tell the patients on Sunday, and then they would tell the public on Monday. That's just MHO (and a bit of wishful thinking).
from the data that I have put together it seems that Avonex + Tysabri are additive and synergistic in blocking T cell migration out of the bloodstream and into body tissues
1. beta intereron reduces expression of VLA-4 on T lymphocytes so they cannot bind VCAM-1 on the wall of blood vessels and leave the bloodstream and enter tissues 2. beta interferon also dramatically increases the expression of a soluble form of of VCAM-1 that kind bind VLA-4 and block the ability of T-cells to leave the blood stream 3. tysabri directly blocks VLA-4 and keeps T-cells from leaving the bloodstream and entering tissues
*** so combo therapy is additive and synergistic in further reducing the numbers of T cells that leave the blood stream *** BUT IF THE ABILITY OF T-CELLS TO LEAVE THE BLOODSTREAM WAS TOO SEVERELY COMPROMISED THEN YOU WOULD HAVE SEEN VIRAL REACTIVATIONS OF ALL OF THE LATENT VIRUSES IN THE CLINICAL TRIAL - AND THERE WAS NO DATA SUGGESTING THAT TYSABRI + AVONEX PATIENTS DEVELOPED RECURRENT HSV-1 COLD SORES OR GENITAL SORES, NO EVIDENCE OF REACTIVATION OF EBV CAUSING MONONUCLEOSIS TYPE DISEASE, NO REACTIVATION OF VACCINIA TO CAUSE SHINGLES, NO CASES OF CMV - THEREFORE ALTHOUGH TYSABRI + AVONEX HAS AN ADDITIVE IMMUNOSUPPRESSIVE EFFECT IT CANNOT BE THE ENTIRE CAUSE - THAT TIS WHERE THE GENETIC PREDISPOSITION OF PATIENTS COMES IN
another interesting point that is not appreciated by most - when you give avonex + tysabri the tysabri clearance from the blood is reduced by 30% - but was no reduction in dosage of tysabri in the tysabri + avonex patients - that meant that over time the tysabri concentration in the blood of patient continued to rise month after month resulting in an ever higher level of tysabri and a greater and greater T cell immunosuppression - this is another risk factor***
ONE MORE THING - PML DOES NOT TAKE ANY TIME PERIOD TO DEVELOP - IF YOU LOOK IN THE LITERATURE - AFTER IMMUNOSUPPRESSION CASES CAN DEVELOP AS QUICKLY AS 7 DAYS - SO PLEASE JUST GIVE THE TIME THEORIES A REST - PML DEVELOPS WHEN YOU HAVE ENOUGH RISK FACTORS, THE VIRUS IS PRESENT, THE IMMUNE SYSTEM IS NOT - AND THEN IT ONLY OCCURS IN A VERY SMALL NUMBER OF PATIENTS
THAT IS WHY IT IS QUITE CLEAR THE TYSABRI MONOTHERAPY WILL BE PROVEN TO BE OF NO RISK FOR CAUSING PML BECAUSE IT WORKS EXACTLY THE SAME WAY AS BETA INTERFERON
Well god knows we love to throw a drug on top of a drug on top of a drug. How else would these pharma companies make money...My question is, whats on the market for the JC Virus ....hell, whats one more pill if these drugs work.