MRTCs, Masking/Suppressing, and Some Thoughts

A board to discuss Tcelna as a treatment for Multiple Sclerosis

MRTCs, Masking/Suppressing, and Some Thoughts

Postby IHaveMS-com » Sun Dec 16, 2007 8:03 pm

Hi to all,

I know I have said this about 100 times, but here it is again. The hope for Tovaxin is that it will halt the progression of MS. If the body is no longer under attack, it may be able to repair some of the damage and restore some lost abilities. This might be a good time to reread my first post on the thread “Results will vary”. http://www.thisisms.com/ftopict-4133.html

Every time when my series of treatments have ended and I am tested again for MRTCs, I always have had some MRTCs and new vaccine is made. Before I am tested for MRTCs and before giving a bag of blood for making vaccine, I avoid alcohol. I have read that alcohol compromises the immune system.

I assume that testing positive for MRTCs is greatly affected by the waxing and waning of RRMS and anything someone might have been taking that could mask the MRTCs. I wish I knew all of the things that can mask MRTCs. If I did, I would make sure I stayed away from them especially when it came time to test for MRTCs and when having a bag of blood drawn for making vaccine. Curcumin, which is found in the Indian curry spice turmeric, can mask MRTCs. Stay away from the list of drugs that Lars posted http://www.thisisms.com/ftopic-3826-0.html It is about midway down the first page.

When I first started looking into masking MRTCs, I thought masking was a means that prevented the MRTCs from being detected. That is partially true. I think masking/suppressing might be better terminology. The drugs in the list above suppress the immune system. If they are able to suppress the production of a particular MRTC below the point at which it can be detected, it has essentially masked that particular MRTC.

About now, a light bulb should be going off in your head. If these drugs suppress the production of MRTCs, why don’t people take a bunch of them and suppress the MRTCs. I assume the answer is – that would just be a weak form of what the CRAB drugs do. When the immune system feels like it, it will produce millions of MRTCs and whatever suppression the drug was doing won’t be the least bit effective against that level of production.

The Tovaxin protocol uses 163 different peptide fragments over 3 of the major myelin proteins to identify an individual’s MRTC set. 109 of these peptides have been found to identify MRTCs. When I started the study, they were using only 6 peptides from one of the proteins for screening.

The initial screening determines if an individual has circulating MRTCs that react with these myelin peptide fragments (called epitopes). A negative result means that MRTCs could not be detected by the assay. The inability of the test to detect MRTCs means that at that time an individual for some reason does not have adequate levels of MRTCs to be detected.

Both people with MS and healthy subjects make MRTCs. In people without MS, the immune system realizes that those cells are "self reactive" and they are not allowed to expand. In people with MS, at certain times and for as yet unknown reasons, these MRTCs are allowed to expand. The body does not seem to have any defense against autoimmune diseases. With self-reactive cells, the body produces them and is not able to realize that they are destructive.

The body produces more than one billion lymphocytes and other immune system cells daily. Since there are approximately only 10 or 20 MRTCs per 1 million WBCs, eliminating them appears to not compromise the immune system, but it does eliminate the pathogenic T-cells that destroy myelin. A flare is when the body produces too many of these bad T-cells.

Tovaxin causes the body to produce memory WBCs that produce T-cells that destroy the MRTCs as they are produced. Until the number of MRTCs is reduced to near zero, they are still floating around and possibly nibbling at your myelin. It is possible that the memory white blood cells that produce the MRTCs might decide to produce several million and overwhelm the vaccine produced T-cells that are eliminating the MRTCs. In that event, you might experience a slight attack, only a guess. Once the MRTCs are at or near zero and the amount of memory WBC that produce the T-cells that take out the MRTCs are at a sufficient level to produce enough T-cells to neutralize a flare, the attacks should stop.

Everyone is going to build protection against MRTCs differently. Everyone is going to have a different rate at which they produce MRTCs. By monitoring a patient's blood, the amount of Tovaxin needed to keep the MRTCs at or near zero can be determined and the appropriate dose and cycle of vaccine can be determined. I assume that during the build up period, while there are still MRTCs floating around, a patient could have an attack.

Two people who were in Dr. Zhang's T-cell vaccine study at Baylor in the late 1990s no longer produce MRTCs. They will still need to be monitored, but at this point they are in remission. This could happen to some of the patients in the current study. I believe I saw in the protocol that if that were to occur, the patient would have his/her blood checked every 2 months.

Tovaxin selectively eliminates only the MRTCs that mistakenly attack myelin. It does not interfere with any other T-cells, has no effect on the blood-brain barrier, and has no known health risks. Eliminating this small fraction of MRTCs from a person's immune system has little effect on the immune system, but does eliminate the T-cells that cause the destruction of the patient's myelin.

Tovaxin works like other vaccines by making the immune system form immune cells to protect against a disease. The yearly flu shot that many people get makes the body form antibodies against an external invader. Tovaxin makes the body form immune cells against an internal destructive force, the pathogenic T-cells.

A major difference between the yearly flu shot and Tovaxin, is that the antibodies generated by the flu shot and the memory WBCs that continue to produce those antibodies have time to make a sufficient number of disease specific T-cells that prevent the disease from progressing to the point where the patient develops symptoms. Multiple Sclerosis is an autoimmune disease (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.

It takes 10 to 12 weeks to make vaccine from the time the bag of blood is taken, and since it takes approximately 3 treatments to get full protection. The average patient will not be protected for about 28 weeks after the bag of blood. Depending on how many MRTCs are produced during the buildup period, you could be unlucky and have an attack.

I don't want to put any thoughts of concern into your head, but at the end of the year, most, if not all, of the people who were on Tovaxin will be making sufficient MRTCs to make new vaccine. It will not take 28 weeks for those people to regain full protection, but it will be X weeks since their last treatment plus Y weeks to make the new vaccine before they once again have sufficient memory T-cells to control the production of MRTCs.

Since Dr. Zhang was testing a form of Tovaxin in the 1990s and the new studies have been on going since 2003, the scientists have determined the dosing schedule that the vast majority of patients will need to halt the destruction of myelin. Since there can be epitope shifts in a patients MRTCs, I assume there must be a window in which there is no vaccine. This would allow the scientists to be able to test the blood to see if the immune system is still producing MRTCs and if there is any new ones, epitope shifts.

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.

Tovaxin will evolve. It is patient specific, and as such, each patient will need a certain number of treatments per year to keep the memory T-cells at a sufficient level to control whatever amount of MRTCs are produced.

Some other things to consider – a little exercise before the injection and no NSAIDs after the injection would probably be beneficial.

I hope everyone has great disease reversal, but the bottom line is, if going forward, you are never worse than your worst day in the past, Tovaxin is working.

From what I can tell, the people in the extension study wake up each morning looking for what function they have regained today. I hope it works that way for everyone, but that is not what the hope for Tovaxin is. Its purpose is to stop the attacks.

If when you wake up each day, you do not sense any regained function, you can be disappointed in your body's inability to restore itself. If on the other hand, you wake up and are feeling more disabled than you were at your worst point, then you can be disappointed in Tovaxin.

Some things to consider if your are in the Tovaxin trials:
1. It isn’t an attack unless it lasts for more than 4 days.
2. I will not consider my EDSS to have changed unless it stays changed for 2 or more consecutive assessments.
3. I will remind myself that the hope for Tovaxin is to stop the attacks. Any restoration of lost functions is up to my body.
4. I will not expect to sense any difference until at least 100 days after my first injection of the “real stuff”, and it is possible that it might take 4 treatments plus 10 days for my immunity to get up to a sufficient level to fend off attacks. http://www.thisisms.com/ftopict-5631.html
5. If I get some lost function back and I lose it again, I won’t think that I am having an attack but rather, that the body needs to do some more restoration to the nerves that control that function. But, if I get back some lost function and that restoration lasts for more than 8 weeks without interruption, it is for real, and in that case, if you lose the regained function after 8 continuous weeks of having it, discuss that with your neurologist.
6. There may be a point during the 100 days that you sense things are starting to get better. Use the day before you get that feeling as your baseline. No matter what ups and downs you encounter going forward, if you don't drop below your baseline, Tovaxin is working.
7. This is a patient-specific vaccine and there are a lot of other patient-specific rules. And most important of all, results will vary
http://www.thisisms.com/ftopict-4133.html
Last edited by IHaveMS-com on Sat Jun 14, 2008 7:50 am, edited 2 times in total.
Best regards, Tim

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.
User avatar
IHaveMS-com
Family Elder
 
Posts: 213
Joined: Tue Jun 07, 2005 3:00 pm

Postby hmtucker » Tue Dec 18, 2007 8:43 am

Tim,

I have some questions for you. These all relate to the schedule that we in the phase IIb study have been on. We received injections at 0, 4, 8, 12 and 24 weeks. What is your Tovaxin vaccination schedule? Is your schedule determined by your monthly blood draws? Let's consider a hypothetical situation here. If you are on the same schedule as above and they find a sudden rise in MRTCs in your 40 week blood draw do they call you in for a "booster" vaccination or do you not receive any more vaccinations until the next years cycle with the new Tovaxin formulation?

Thanks,
Mike
User avatar
hmtucker
Family Elder
 
Posts: 100
Joined: Tue Nov 28, 2006 4:00 pm
Location: Versailles, Kentucky

Postby IHaveMS-com » Tue Dec 18, 2007 7:44 pm

Hi Mike,

I had to sign a new consent form last week. I have finished one extension and am now in a second extension. Since your study and mine are different, I will list a few things about the study I am in. The extensions for each of the studies may be similar or my have some significant differences.

The title of my extension is, "An open-label, dose-escalation study of T-cell vaccine in Multiple Sclerosis". My first treatments were at weeks 0, 4, 12, and 20, and were at the low dose of 6 - 9 million cells. I received 4 treatments and then nothing for 32 weeks at which time blood was drawn for new vaccine. Your study had 5 treatments and then nothing for 28 weeks at which time blood was drawn for new vaccine.

After the mid-dose was shown to be safe, I was moved into the mid-dose of 30 - 45 million cells, and that is where I will remain. Those people who are in the high dose group of my study will continue to receive the high-dose (60 - 90- million cells) until Tovaxin is approved.

What is your Tovaxin vaccination schedule?


I receive vaccine at 0, 8, 16, 24, and 32, five treatments at 8-week intervals.

Is your schedule determined by your monthly blood draws?


No, it was predetermined. I assume the schedule is based on the knowledge that they are accumulating.

Let's consider a hypothetical situation here. If you are on the same schedule as above and they find a sudden rise in MRTCs in your 40 week blood draw do they call you in for a "booster" vaccination or do you not receive any more vaccinations until the next years cycle with the new Tovaxin formulation?


Hypothetical questions generate hypothetical answers. After receiving the 5 treatments, if the study doctor feels that your MS symptoms have gotten worse and the worsening lasts for more than 12 weeks and you continue to have detectable MRTCs, you may be able to receive additional retreatments. I guess that is not very hypothetical since I am quoting that from my new protocol.

Hypothetically, the company does not want you to have any attacks, and if that means giving you extra vaccine, they will. Some people are going to produce more MRTCs than others. We are all lab rats whose results will help determine how Tovaxin is dosed once it is approved. If there is a problem once you are on Tovaxin, they will want to fix it. If it requires modifying your current protocol, they will probably modify the protocol.
Best regards, Tim

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.
User avatar
IHaveMS-com
Family Elder
 
Posts: 213
Joined: Tue Jun 07, 2005 3:00 pm

Postby Lyon » Tue Dec 18, 2007 9:10 pm

.
Last edited by Lyon on Wed Nov 30, 2011 7:37 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Postby IHaveMS-com » Tue Dec 18, 2007 9:21 pm

Hi Bob,

will the extension follow that same pattern and include the 28 week waiting period?


As I said above, the extensions for each of the studies may be similar or my have some significant differences. Loobie will have to let us know what the protocol is. I believe he will sign that prior to getting his first treatment in the extension study.
Best regards, Tim

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.
User avatar
IHaveMS-com
Family Elder
 
Posts: 213
Joined: Tue Jun 07, 2005 3:00 pm

Postby Lyon » Tue Dec 18, 2007 9:41 pm

.
Last edited by Lyon on Wed Nov 30, 2011 7:36 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Postby IHaveMS-com » Sun Feb 17, 2008 6:39 pm

Hi to all,

If you are going into the extension study or thinking about being in the phase III study, you should read my post http://www.thisisms.com/ftopict-4868.html There is a buildup period where each successive dose of vaccine stimulates the body to produce more T-cells to eliminate the MRTCs. Each injection also stimulates the immune system to produce memory WBC that continue producing the T-cells that remove the MRTCs as the body mistakenly produces them. You will start building protection with the first injection, but it may take 3 injections to get your immune system up to a level that can handle any large output of MRTCs, an attack.
Best regards, Tim

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.
User avatar
IHaveMS-com
Family Elder
 
Posts: 213
Joined: Tue Jun 07, 2005 3:00 pm

Postby Lyon » Sun Feb 17, 2008 6:56 pm

.
Last edited by Lyon on Tue Nov 29, 2011 7:17 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Postby Lars » Mon Feb 18, 2008 7:09 pm

Tim,
Wow, when you show up, you do it up right. Nice to see you're still checking in on us. We had to elevate Bob to Commander in Chief, did I mention welcome back.
Ciao,
Lars
Lars
Family Elder
 
Posts: 433
Joined: Wed Mar 21, 2007 4:00 pm
Location: Durango, Co

Postby Lyon » Mon Feb 18, 2008 8:15 pm

.
Last edited by Lyon on Tue Nov 29, 2011 7:15 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Postby Lars » Mon Feb 18, 2008 10:25 pm

Bob,
How'd I know you would catch that. We would never impeach you. Can't say my feelings run that high for our other Commander and Chief.
Lars
Lars
Family Elder
 
Posts: 433
Joined: Wed Mar 21, 2007 4:00 pm
Location: Durango, Co

Postby Lyon » Tue Feb 19, 2008 7:08 am

.
Last edited by Lyon on Tue Nov 29, 2011 7:10 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Postby Lars » Tue Feb 19, 2008 7:48 am

Well put.
Lars
Lars
Family Elder
 
Posts: 433
Joined: Wed Mar 21, 2007 4:00 pm
Location: Durango, Co

Postby JanethePain » Tue Feb 19, 2008 9:01 am

Lars wrote: Well put. Lars


I was wondering how long it would take you guys to drift into political stuff. :lol: Don't get me wrong; I'm glad you did. A day without political "discussion" is worse than a day without sunshine. :D
Jane the Pain
User avatar
JanethePain
Family Elder
 
Posts: 223
Joined: Wed Jun 13, 2007 3:00 pm
Location: Historical Glendale, OH: Home of the Squirrrels

Postby Lyon » Tue Feb 19, 2008 2:16 pm

.
Last edited by Lyon on Tue Nov 29, 2011 7:09 pm, edited 1 time in total.
Lyon
Family Elder
 
Posts: 6063
Joined: Wed May 03, 2006 3:00 pm

Next

Return to Tcelna (Tovaxin)

 


  • Related topics
    Replies
    Views
    Last post

Who is online

Users browsing this forum: No registered users


Contact us | Terms of Service