March 12, 2007

Reversing type I diabetes (insulin-dependent diabetes) in humans

by

Sunday, March 12 – 9pm est.
Dr. Bernie Tuch Director, Diabetes Transplant Unit, Prince of Wales Hospital in Sydney, Australia
Topic: Reversing type I diabetes (insulin-dependent diabetes) in humans
www.diabetes.unsw.edu.au

Dr. Tuch is the Director of the Diabetes Transplant Unit at the Prince of Wales Hospital in Sydney, Australia and a Professor of Medicine at the University of New South Wales, Australia. The trial recently commenced with encapsulated human islets injected into the abdomen is the second clinical trial I have helped pioneer. In the mid 80’s I led the group in Sydney that transplanted human fetal pancreas into people with type 1 diabetes. The Unit I direct is now looking at other potential cellular therapies for diabetes, which include using embryonic and adult stem cells.

[Jon]: Hello everybody, and thanks for joining us tonight! [Jon]: Welcome everybody to the DTF Chat Room

[Jon]: Tonight, we are chatting with Dr. Bernie Tuch, Director of the Diabetes Transplant Unit, Prince of Wales Hospital in Sydney, Australia.

[Jon]: Tonight’s topic will be Reversing type I diabetes (insulin-dependent diabetes) in humans.

[Luc]: Welcome Dr. Tuch, I’m very excited and encouraged by your progress in research and transition into human trials. Thank you for pushing forward to make this happen. I’m also curious about the correlation between the alginate capsules, iodine and post transplant thyroid studies. Has there been anything done here yet to determine long term effects?

[Jon]: Dr. Tuch is the Director of the Diabetes Transplant Unit at the Prince of Wales Hospital in Sydney, Australia and a Professor of Medicine at the University of New South Wales, Australia.

[Ellen]: Dr. Tuch , I’m sure we’re all on the edge of our seats to know if you have any results yet from the patients recently infused with encapsulated human cadaver islets

[Dr. Bernie Tuch]: Hello everyone. A pleasure to be talking with you. 9pm your time on Sunday; 1pm Monday Sydney time.

[Dr. Bernie Tuch]: Ellen, we have started the trial and have done our 3rd transplant. In the interests of allowing the trial to be done properly, it is proposed that an announcement will be forthcoming either when the first patient is off insulin, or the end of the trial in 12-18 months, whichever comes first.

[Ellen]: Do you hope to have a poster presentation at ADA this summer?

[donna]: Can you tell us some stats on the transplant patients? Age, length of time as diabetic, why you chose them?

[Dr. Bernie Tuch]: Sorry, let me qualify the last statement – off insulin for at least a month with scientific proof this is due to the transplant. The trial started 3 weeks ago today.

[Luc]: I’m very excited and encouraged by your progress in research and transition into human trials. Thank you for pushing forward to make this happen! I’m also curious about the correlation between the alginate capsules, iodine and post transplant thyroid studies. Has there been anything done here yet to determine long term effects?

[AllieB2]: Dr. Tuch– how did you know to look towards an element of seaweed to encapsulate islets?

[Dr. Bernie Tuch]: Recipients are adults (up to 55 y) with type 1 diabetes, < 70 kg and BMI < 25, with absolutely no C-peptide in blood or urine

[Dr. Bernie Tuch]: Good question, Luc. The capsules are made from alginate, a product from seaweed. This has nothing to do with the iodine content of seaweed which you were referring to.
[Luc]: What is the “life expectancy” of the alginate capsules?

[Dr. Bernie Tuch]: The idea of using alginate microcapsules has been around for 20+ years. What has changed over the years has been the purification of the alginate and an examination of its properties. There are a number of groups in different countries all working on various versions of microcapsules.

[Dr. Bernie Tuch]: Luc, a group in New Zealand has shown capsules can last for at least 9 years. Experiments we have conducted in mice show survival for at least 1 year.

[Luc] : Any new stats on the effects of cytokines on the islets in the alginate capsules?

[donna]: What do you do with the capsule? Implant it?

[Ellen]: Is the immunosuppression temporary with this protocol?

[diajoe]: Are the capsules infused into the liver?

[AllieB2]: if the encapsulation protects the islet from an autoimmune attack: in theory, would you be able to use porcine islets instead of human islets?

[Dr. Bernie Tuch]: Luc, good question again about cytokines. Clearly they can get into the islets, and of course this will result in a deleterious outcome. We do not see an inflammatory response around the capsules in animal transplants; in the human trial we are using mild anti-inflammatory agents and anti-oxidants in tablet form

[Luc]: If you require 2-4 donors per transplant recipient—and it’s already clear that your research is based on organ supplies– has any consideration been given to evolving a means to procure islets from live donors? Much in the same way blood or partial lung donations are done, perhaps a small sampling from 12 – 20 donors could provide the same source results for the trial without rendering the donors diabetic in the process.

[dave]: Why not do a trial with a very significant quantity of islets transplanted, > 1M, and then back off instead of ramping up

[Dr. Bernie Tuch]: Ellen – no immunosuppressing is used. Diajoe, the encapsulated cells are injected directly into the abdominal cavity. They may rest in part on the surface of the liver but there is no infusion into the liver .

[diajoe]: Would a patient be a candidate if they previously had a cancer that was treated with Leukine?

[newg]: wow, lots of people in here tonight!

[AllieB2]: Supposedly one hemisphere of the human spleen generates cells that can “become” islets….or did I make that up? I thought I read it somewhere

[Dr. Bernie Tuch]: Luc. Live donors may b a possibility once it has been established that encapsulated human islets consistently normalize blood sugar levels in diabetic human recipients without immunosuppression. We don’t know if this can be achieved in humans, although it has in animals. That is the question which the trial is designed to commence answering.

[Luc]: Are you aware of the work that Dr. Anthony Atala is doing at the Wake Forest Institute for Regenerative Medicine? His team is engineering pancreatic cells that, when inserted into a faulty organ, will make insulin. Could there be a way your studies could partner with his and expedite a means to a cure?

[Dr. Bernie Tuch]: AllieB2. There is some discussion about beta cells being produced in the spleen. We are giving consideration to using this site amongst others to implant the encapsulated cells.

[diajoe]: The University of Miami School of Medicine in Miami, Florida has successfully transplanted beta cells in more than 20 patients

[AllieB2]: Dr. Tuch– how much did it cost to get your trials underway? and how much will it cost to complete?

[AllieB2]: diajoe– U of Miami uses immunosuppression treatments (I think)

[Ellen]: Are you trying the same encapsulating alginate with porcine islets in animal studies?

[Dr. Bernie Tuch]: Luc, injection of insulin-producing cells into the pancreas is a logical step, but there are dangers in doing so. 99% of the pancreas produces enzymes which are involved in digestion. The danger is that release of the enzymes will cause lysis of the transplanted cells.

[dave]: Is your alginate the same as Dr Califore’s or is it some modification?

[Dr. Bernie Tuch]: AllieB2. Cost is always a problem in these trials. The cost is much less than the more traditional method of using unencapsulated islets since no anti-rejection drugs are needed. Estimated cost per patient for materials is ~$24,000 per patient. At present, funds are coming mostly from private sources.

[Dr. Bernie Tuch]: Ellen, we are experimenting on encapsulated pig islets at present, but are not ready for human trials with these.

[Ellen]: Do you think the gov’t of Australia will approve xeno trials in the near future? I have my doubts unfortunately. Certainly insulin is not a cure. And here is obviously a finite and very limited amount of cadaver islets.

[Dr. Bernie Tuch]: Dave. Professor Calafiori has been a catalyst to help push us in getting our trials underway. So, a big thank you to him. His capsules and ours are different. At present it is not known which is “better”. We are comparing notes.

[Luc]: Regarding Ellen’s question on encapsulated pig islets, what do you need to get ready for human trials?

[Dr. Bernie Tuch]: Ellen, with time and patience most obstacles will be overcome. I would like to believe the current moratorium on using pig islets will eventually be lifted, once good data become available to convince the relevant Committee of the potential benefit of the procedure.

[Dr. Bernie Tuch: Luc. Human trials require vision, a source of donor pancreases, funding, suitable recipients, and solid animal data, and a strong drive to make it happen.

[Ellen]: Another area of research I noticed you’re involved in , is embryonic stem cell research. How is that work progressing?

[Dr. Bernie Tuch]: My Unit is progressing on several fronts. We have produced an embryonic stem cell line under animal-free conditions, so that potentially it can be used in humans. We and others are trying to differentiate embryonic stem cells into true beta cells, an elusive goal at present. However, we are trying using some novel approaches.

[AllieB2]: Dr. Tuch- is there any way you could propose clinical trials for your research here in the US?

[Dr. Bernie Tuch]: AllieB2. I have no doubt such trials will take off in the US once there is irrefutable proof by several investigators in the benefit of the procedure for treating type 1 diabetes.

[AllieB2]: 🙂 thank you

[Ellen]: Do you feel Dr. Hwang’s fraud has hurt the public view of the benefits of embryonic stem cell research?

[Ellen]: Do you feel the Edmonton protocol and spinoffs of same should be halted since they do not produce long term success and the risks from the immunosuppressants is great? I personally feel we’ve learned all we should from them and the limited funding for research should go towards safer protocol.

[AllieB2]: I agree with you, Ellen!

[Dr. Bernie Tuch]: Ellen. The potential benefit of stem cells, whether embryonic or adult, is not dependent on any one person. What Professor Hwang reported was that nuclear transfer could be successful in humans, just as it is in animals. With time, it is only to be expected this will be shown by other groups.. So, I don’t think what happened in Korea will have any long lasting adverse effect on the field.

[Kelly]: OK….I’ll ask. I am 44, been T1 for 38 years. In your opinion, will I see a cure in my lifetime or is it further off than that? I am so far a healthy T1 with no major complications.

[dave]: Dr Tuch, I understand the problem with encapsulation has been insufficient oxygenation & nutrients not getting to the cells. The DRI has recently published research stating the islet cells in humans need to work in close proximity to other specific cell types. Has any work been done to place these cells in some kind of nutrient enhanced capsule or shared with other cell types?

[Dr. Bernie Tuch]: Ellen. A provocative question re Edmonton. The Edmonton protocol, or modifications of it, are the best we have at present for people with type 1 diabetes who want a means of replacing their insulin-producing cells. Yes, there are issues such anti-rejection drugs and limited survival after 5 years. If encapsulated human islets can achieve a similar outcome without anti-rejection drugs, this will be wonderful. and a step forward.

[Dr. Bernie Tuch]: Kelly. In my life time I am predicting that an appropriate therapy will be available, and I am 55.

[Ellen]: Is there any proof of spread of porcine retroviruses to humans? Do you think the objections of the nay sayers are founded or unfounded?

[Kelly]: YAY!!

[Dr. Bernie Tuch]: Dave. Islets are clusters of insulin-producing cells in connection with other cell types. The possibility of enhancing nutrient exposure is being discussed, and protocols are being developed to try and achieve this, in animals in the first instance.

[AllieB2]: Dr. Tuch: as a diabetic, type I, thirsty for the cure….is there *anything* I can do to help encourage the trials you are currently conducting?

[Ellen]: Does your research facility work independently or do you collaborate world wide with other researchers? I wondered if you discuss your embryonic stem cell line with Dr. Dominguez-Bendala in Miami at the DRI?

[AllieB2]: money? word of mouth? like I said *anything*?

[Dr. Bernie Tuch]: Ellen. The data from the CRC in Atlanta showed no evidence of spread of porcine retroviruses into humans transplanted with or exposed to pig cells. To continue to use the argument that pig retroviral infections will occur in human recipients is therefore not borne out by existing knowledge. It will pay to be cautious though and put appropriate checks and balances in place when pilot trials in humans re-start.
[Marcia]: Sorry, I’m trying to figure out how to get past posts so I don’t ask something that has already been discussed. My 22 year old daughter was dx’d at age 2–we seem to have better meters and some designer insulin but I don’t see much else that has changed in 20 years. certainly not that “cure in 10 years” we kept hearing about.

[Luc]: Thank you again Dr Tuch for taking the time to address our questions. I will be following your progress very closely. I wish you tremendous success as your trial work continues.