You are spot on with that one. I agree totally. It hurts like hell to exercise now, but it's like not doing your PT after knee surgery. You 'gotta do it if you want it to work. I agree about how it will always be there with heat and exertion. Tim comments on that alot. That even though he isn't having fresh disease activity, exercising makes him feel like crap, as it does most of us. Punchy just had a thread about it in General Discussion and we were talking about how hard it is to stay motivated to continue because of how bad you feel when you are done working out.
I mean hell, the endorphin release and INCREASED energy used to be the benefits of exercise and those are easy to get motivated for. Just the thought of feeling stronger is incentive, but it's hard to look forward to stuff that hurts. All that being said, I think it is the single most important thing to do if, like you said, you think you have stopped the progression.
In the thread for the 100 plus days club, question number 3 -- "How have you felt from the end of the study until reaching the 100 plus days mark?" is pointed directly at your experience. You felt much better, saw improvement as you continued getting injections, and saw a reoccurrence of symptoms after the treatments stopped.
I don't think that a burning sensation is indicative of getting Tovaxin verses placebo. I have never sensed a burning feeling, but that is just my experience. Since Tovaxin is your own cells (expanded in the lab) being injected, you probably would have experienced a burning sensation from a placebo injection as well. Since you had quite a few areas of disease reversal, it seems likely that you were on Tovaxin.
Since Multiple Sclerosis is an internal disease that at any time can cause the body to produce millions of MRTCs. The re-dosing process that Tovaxin uses keeps the immune cells at a level sufficient to be able to respond to an increased production of MRTCs, and thereby prevent an attack. Keeping the immunization level high enough to prevent an attack from an internal source is much different than having sufficient disease protection from an external source.
Using chicken pox as an example, the antibodies generated by the chicken pox and the memory WBCs that continue to produce those antibodies, have time to make a sufficient number of chicken pox specific T-cells that prevent the disease from progressing to the point where the patient develops symptoms. Each time you are exposed to someone with chicken pox, you reinvigorate your immune system; specifically to continue producing chicken pox killer T-Cell and memory T-Cells to produce more when necessary.
Since it seems likely that you were receiving Tovaxin, and I believe your protocol is to receive 5 injections over 7 months. That means you had no treatments for 5 months and adding to that the 10 to 12 weeks to make new vaccine from the time the bag of blood is taken, your level of immunity for MRTCs had approximately 8 months to wax and wane.
If your body continued to produce MRTCs at a high steady rate, that would be like being constantly exposed to chicken pox and your level of immunity would be the same at month 15 as it was at month 7. If on the other hand at month 7, your body took a rest from producing MRTCs, you immunity would slowly start to diminish. Then if at month 11, 12, 13, etc. you body decided to produce a large amount of MRTCs, this could overwhelm your slowly declining number of memory T-Cells, which were programmed to produce T-Cells that would kill the MRTCs.
Light bulb time -- If you had been producing a high steady amount of MRTCs, which would keep your immune system really fired up against MRTCs, is it possible that your MRTCs would remain at or near zero and you would not have detectable MRTCs -- sounds probable to me.
Another light bulb, but probable not as obvious -- When you first receive Tovaxin, you have lots of circulating MRTCs. As the battle rages on and you get successive treatments, the Tovaxin induced army brings the amount of MRTCs to at or near zero. This is likely to occur at the 100th day. Successive treatment will produce more memory T-Cells, but if you are not actively producing MRTCs, their number will start to decline. Since you don't know when the body will decide to produce lots of MRTCs, that is the reason for getting booster treatments or starting a new round of injections.
This is an individualized treatment and for the average patient, the dose regiment in the protocol will work just fine. For some people this may wipe out the MRTCs to the point that they will only need to be monitored going forward. For others, the amount of treatments necessary to keep the number of MRTCs at or near zero will need to be more than 5 treatments per year. This is a study. You are the lab rats. They want to determine what would be a typical treatment for the general MS population, and learn how to determine the specific treatment schedule for those who stop having detectable MRTCs and for those who have symptoms returning before the next series of treatments starts.
All that being said, a person not on Tovaxin at best can hope that what they are taking, the CRABs, Tysabri, or something else, has down regulated their immune system so that it does not produce sufficient MRTCs to cause an attack. They do not have any internal defense against MRTCs. There is nothing in their immune system to eliminate MRTCs. When the body produces them, they will attack the target that they have been programmed to eliminate, myelin. The hope for the current treatments is to cause the body to produce fewer MRTCs, but as a consequence of that action, the body will also produce less protective T-cells
I have just returned from Houston and treatment number 22. I didn't post about treatment 21. I assume as always, that I will not have an injection site reaction. If I do, I will post that fact, otherwise, I will be back at the end of June to see how the 100 plus day thread is going.
The people moving into the extension must not expect any disease reversal, only hope that the attacks will stop. If you think on day 101 you are going to feel like you did pre-MS, I am sorry to say you are setting the bar too high.
In 2001, my family helped fund the startup of Opexa. My father served on the Board of Directors of PharmaFrontiers, now Opexa Therapeutics, until the company completed a successful 23-million dollar financing round.
Another thing that I think should be brought up is the idea of "epitope shift." In going through some of the published work from Opexa I remember that they make a reference to epitope shift for people moving from one round of Tovaxin vaccine to the next round of Tovaxin vaccine. In a nutshell what this means is that on day 0 your immune system is making a set of MRTC's that bind to certain parts, or epitopes, of myelin (and the other proteins that they screen against) but by day 365 your immune system has changed somewhat and it now makes a set of MRTC's that bind to different epitopes of those proteins. So, it is possible that the Tovaxin vaccine has knocked down your original set of MRTC's down to zero but your immune system is now making a new set of MRTC's that can cause problems. This is the rational for making a new vaccine each year rather than just giving more injections of the original vaccine that was made for you.
As both a scientist and a participant, those are data that I will be very interested to hear about when they release the results from the IIb phase. I feel I am in a similar situation to Rumblebee in that for the first 8 months of the IIb things were VERY stable for me with some very noticeable improvements in my situation (I have described these in other posts so I won't elaborate here). Placebo effect...... possibly but I sure as hell never had a placebo effect from Betaseron or Copaxone! However about 3 months after my last Tovaxin injection I had a small but significant flare and I am still having trouble climbing back to where I was pre-flare. I have a sneaking suspicion that this is due to an epitope shift in my MRTC profile. Again, as a science nerd I would love to see the results of my MRTC profile from the blood that they siphoned at each visit. It should be readily apparent whether or not not my MRTC profile had changed from day 0 until the time of my flare up.
I am also very interested to see if the protocol changes in the extension study. If it is clear that a persons MRTC profile has changed during the vaccination schedule and their immune system is now pumping out lots of MRTC's to epitopes that their current Tovaxin preparation can not address will Opexa direct that a new blood procurement should be done to produce a new Tovaxin preparation even though the year is not completed?
Inquiring minds and all......
Thanks for elaborating like that. For some reason I completely understood what you were saying! I've tried to understand what people are talking about with the epitopes and that and never quite grasped it. Good explanation. I'm sorry to hear you had a flare. Those suck when you are doing well (duh), and I hope you get back to pre-flare conditions soon.
That constant feeling that something just isn't right, I think of as "submerged". Try and try as I might, I can't get my head above the "water". I haven't felt right for quite some time. Even on the really good days, I am submerged. I can feel it working against me. Everything I do is a little harder than it should be. Submerged. The day that feeling goes away, I will know that I am well.
Good thing we are all fighters.
Since it has been all week (thus over 4 days ), I am going to attempt to describe some of what has been going on with me. It's all been subtle, as we all probably knew it would be since it's not active symptom treatment. My first notice of some improvement was my trip to Atlanta last week. I posted a little bit about it, but quite frankly it was kind of monumental. In recent history (the past 4-5 months) I have had a real issue with walking any distance at all. It used to just 'take me down' so far and I could deal with it. Like I would go from 100% of normal and it would take me down to 50%. The thing about was it would stop at 50%. I could keep up my activity level and I would not go down any further. So I could walk for a while, get down to the 50% level and keep walking, albeit with a very noticeable limp and drag from my left leg. It was always the left and it always started with knee area weakness and would move from the knee area to the calves and hamstrings. Well here more recently, it just kept going down. I would go past 50% and just keep going down until I would have to stop and take a substantial rest. And even after the rest, I still wouldn't get back to my baseline until the next morning.
Well this week has been really good for me and it was even cememted further yesterday and today so far. I noticed I could walk further through the factory before the inevitable tingling and burning, and I noticed I would recover quicker. Now keep in mind that this has been my gradual decline over the past year and a half. I've never felt an aggressive attack, and once the stuff shows up, it has been there full time until last week. The camping trip I had was my low point. There were a few times that I just had to stop where I was and wait, then stumble back to camp and sit for the rest of the day. OK, enough history. Yesterday it was 90 degrees F and muggy. I am in charge of a very disorganized warehouse that me and my team are cleainng out to make room for a new job (yeah!). The warehouse was hell on me because it was literally jammed full of old machinery and special equipment. Anyone who has leg and balance issues knows how hard it is to maneuver through narrow areas; it just wipes you out. Well this place is one big maze, and it was very hot and muggy. My usual stay could only last a few minutes where I would just show my guys what had to be done, and then I would find a place to sit or my dizziness and weakness could cause me to fall and get hurt. There's nothing soft to land on in a used macinery warehouse.
Well we had 4 machines to 'dig out' and scrap. Not only did I stay with my guys, but I actually physically helped. I was pushing stuff out of the way, maneuvering into tight areas, and here's the kicker; I didn't get dizzy.......at all. And for me to push something out of the way is absolutely unheard of in that environment. Well I kept waiting for my legs to go wonky and I kept waiting for my balance to go, and I kept waiting for my eyesight to go, you get the picture. It never happened. No brain fog, no guaze in front of my eyes, no falling over shit. It was amazing. And to boot I was sweating like a whore in church. Being major league heat affected, that was amazing too. All week long I kept being able to do a bit more and a bit more. You guys have to understand that as short as two weeks ago I could not have done a 1/4 of what I did. Don't take me talking about just yesterday as this being this way for only one day; yesterday was just the pinnacle of my recent improvement.
Now here's where it gets really fun for me. I only woke up one time each of the last 4 nights, and before that, much less than usual. When I started noticing a trend I started to pee in a measuring cup. My voids for a long time have NEVER gone over 5-6 ounces, and 6 ounces was maybe once a month. Lat night I voided just over 8 oz.. I decided to keep track today also, and I've done that twice today.
The subtle changes may seem monumental the way I'm describing them because you have to remember, when stuff shows up with me, it's been permanent. I just had to keep lowering the bar of stuff I could do and how well things functioned. This last year and a half has been so discouraging because of all the talk with my Dr. about me probably being SP. Now I know Tovaxin isn't supposed to work on SP, and maybe I'm not SP and just have rreeaaalllly long relapses. Could be I guess, but just remember, I've never had a period where I regained function. Escpecially in the area of balance and dizziness. Granted my progression has been slow, but it's been constant. I'm not going to say "up until now" because it's all very new, and to me, not to be trusted yet. I could be going through a good patch. It's just funny though because I haven't had a patch of relief for quite some time. I can just imagine me coming back on here in a few weeks and saying everything fell back apart. I hope and pray this stuff is working on me, but I'll guess it's going to take some serious time for me to trust any of this. MS is a cruel, teasing bitch and she likes to screw with our hope.
I'm going to a graduation party tonight for my niece and I'm looking forward to it. That's been a long time coming to. I mean you have to do some family stuff, but when you know all it's going to do is make you feel bad, you start to dread obligations like that. My left leg would actually start to feel 'swollen' and rigid doing stuff like that. I mean you know the drill, you can't just show up and find the couch. So I would hang out with my brother in laws and stuff for a bit until my legs started killing me and my knee started buckling. I didn't even feel weak coming down the stairs this morning.
I don't know guys, I almost feel like me posting this is going to make it go away. I know it doesn't work like that, but shit, you don't want to take any chances, no matter how far fetched they may seem. Well if nothing else, I've had a great ten days or so and that's something I could not have said for years. There have been other subtle improvements, but I have to go shower now to get ready to go to a party. I can't believe I'm looking forward to going somewhere and potentially standing around, it's personally unbelievable.