Posted by Sandy Donchess on June 05, 1999 at 00:03:11:
In Reply to: Re: anti-cd40L/anti cd154 posted by Camillo Ricordi on June 04, 1999 at 19:55:07:
Dr. Ricordi,
Thank you so very much for ignoring your "wise collaborators" and allowing Therese to post your response here. (Also, thank YOU, Therese.) I do have some questions and concerns about CD154 therapy, which I have posted here before, and I hope you consider me to be enough of a "decent" TIF participant to answer them. I don't believe I have been negative about what the DRI is doing; I am just nervous about anything that affects my son's or my immune system. They have done us a lot of damage.
I don't know if anyone has ever printed and shown you any of my posts, so here is some background... My 12 year old son was diagnosed when he was 4. He has a number of other medical conditions - severe ADHD, Oppositional Defiant Disorder, allergies and asthma. He takes Adderall, Remeron and Rescon for these. I was diagnosed with Type 1 in 1968 when I was 11. I was diagnosed with minor microalbuminuria last October and take an ACE inhibitor for that. I have extrememly minimal neuropathy and no retinopathy. I was diagnosed with rheumatoid arthritis 10 years ago, and take Naprosyn, Plaquenil and Methotrexate for it. My stated mission in life is to see my son cured of diabetes.
I received the DRI trial participant packet and read it. Some of the documents that were included spoke of donor marrow. I know from the DRI website that islet transplants with donor marrow were/are being done - Jackie Demijohn in Wisconsin was featured. I believe the trial involving islet transplants with donor marrow is a different one than this trial involving CD154. Is this the case?
I read the Proceedings of the National Academy of Sciences report that Dr. Kirk and Capt. Harlan published in 1997, and the article that Capt. Harlan wrote for the Insulin-Free World Foundation. I have tried to find other information, but have failed. My bumbling understanding is that the immune system has a component(s) that recognizes intruders/"not self" and a component(s) that then attacks and tries to destroy them, the costimulatory response. Infusion of CD154 does not block the "recognizer" component; it blocks the "attack dog" component. My understanding is that it is possible that any virus/bacteria/etc. present in the body when CD154 is infused may never again be attacked because the costimulatory response has been "retrained" to not attack it. This could mean that a person couldn't fight off and get rid of colds/flu and other things. The patient exclusion criteria list includes active infections. Is it the case that during CD154 infusion your immune system is told to consider everything in the body at that time "self"?
I've been told that the immune system may have (in my words) different kinds of "attack dog" components, and that some can still fight off infections of the cold/virus type without also attacking the transplanted islets even if infusion of CD154 is done. Is this the case?
The information I've seen indicates that CD154 infusion would be the day before islet transplant, the day of, the day after and periodically for a month or two, then every month for a year or so. It sounds like you would run the risk of not being able to fight off any infection/"non-self" thing present in your body on those days because of this. Is this the case?
I also have read that none of the monkeys tested have shown any signs of infection. This may sound stupid, but have the transplanted monkeys been surrounded by sneezing, coughing non-transplanted and infused monkeys to see how the transplanted ones do?
A researcher I recently spoke to (if you email me privately - donsa1_AT_dallas.net - I'll give you the details) said that anyone who undergoes an islet transplant at this time will experience failure because of the autoimmune process. This researcher said that anything NOT done with NOD mice or BB rats was essentially to be disregarded. This researcher indicated that the autoimmune process was the problem. I was pretty upset to hear that... Can you tell me your thoughts on what I was told?
Given that I have rheumatoid arthritis, could CD154 "retrain" my immune system to NOT attack me? That would be great. Diabetes brings enough problems, never mind that my arthritis brings me constant mild to severe daily pain.
I am also curious as to how the DRI encapsulation research is going. As I have posted here, encapsulation seems to me to be such a non-invasive thing in that the immune system is not involved. Again, I'm afraid of anything that could interfere with my son's or my immune system. What can you tell me/us about DRI's encapsulation efforts?
At this point, I'm in no way concerned about cost. I'm concerned about islet supply, which everyone knows is a problem. Is there anything going on now that you think will bring about a sufficient supply of islets? I believe Type 2 folks would benefit greatly from islet transplants and perhaps medication to decrease insulin resistance. Am I wrong?
Assuming the DRI trial is successful, do you plan on expanding those trials to other parts of the U.S.? If so, when might that be done? Will the DRI do trials on children? Those of us who are adults can participate now if we make the inclusion criteria and can relocate/be close to the DRI and are selected. But I think the vast majority of us are interested because of our children. Can you tell me/us anything about children?
I have also posted that even if these trials are wildly successful, more will have to be done. Many of the press reports I've seen have quoted you or Norma as saying so. What else needs to be done?
I apologize for being nitpicky and anal-retentive. I believe that at least some of my questions are shared by others, and my hope is to get answers to as many of them as possible.
Again, thank you so very much for your post.