Islet Cell Regeneration and the gene INGAP, Part 8
Date: January 28, 2002
Moderator: Deb Butterfield
Subject: Islet Cell Regeneration, Part 8
Guest: Dr. Aaron I. Vinik, Director, Strelitz Diabetes Research Institute, EVMS
Appearing on: www.diabetesstation.org
Deb Butterfield
Just last month, Dr. Aaron Vinik from the Strelitz Diabetes Institutes in Norfolk, Virginia, announced that his research has reached human trials. Dr. Vinik spearheaded the discovery of “ilotropin” a chemical substance that can re-awaken the potential of cells to produce insulin, and the INGAP gene, a protein responsible for this reawakening. Tonight we are honored to welcome Dr. Vinik to Diabetes Station.
Bill_O
Is it too early to discuss the human trials?
Dr. Vinik
It is not too early to discuss the human trials. They are intended to establish that INGAP may be given safely to human beings, just as it was in the animal safety studies.
Alabama Pumper
What are the anticipated side effects of INGAP Peptide?
Dr. Vinik
Alabama, we have seen no side effects of INGAP thus far. We have tested it in doses that far exceed the anticipated doses in the clinical trials, and it has proved remarkably safe.
Bob Wallach
Arthur and Deb hello. Can you give us some insight as to whether there has been any response so far (in the toxicity testing of INGAP) to the Peptide, manifested in any change in the patients’ diabetes? I know the dosages are small, still, any responses? Also, Arthur, could you comment on the effect of the Peptide on nerve restimulation.
Dr.Vinik
Hello Bob. It’s so nice to have you on board. So far even in large doses, there appear to be no side effects, but it may be early days. We have not included any nerve stimulation tests in this study since it is not designed to show any change. Clearly, if down the road we are successful in reversing diabetes, then the nerve stimulation as well as kidney and eye functions becomes a necessary part of the studies.
Jim
Very glad to hear that nerve and kidney stimulation are being considered for future study!
Mary
Is there anything published regarding the results of your animal trials, and if so, where can we read about it?
Dr. Vinik
Certain publications on the animal trials are available from GMP or the Diabetes Institutes Foundation. The studies on safety, etc. have not been published but were required by the FDA before approving the clinical trials.
Deb
We will have an article about Dr. Vinik’s work in our upcoming issues of Insulin-Free Times, our online magazine.
Jim
How do we apply for participation?
STC
Dr. Vinik, what is the expected result at the conclusion of the Phase 2 study?
Alabama Pumper
Dr. Vinik, I am excited about your research. How does one go about participating in your clinical trial, and approximately what is the time frame for participation?
Dr. Vinik
You apply for participation by contacting gmpcompanies.com. The expected result at the end of Phase 2a is that the compound is safe to give to humans and that within the realms of reason, there is some indication of a trend in the right direction.
Ruth
When will the safety trials be complete? What are the objectives of Phase 1 and Phase 2a trials?
Dr. Vinik
Ruth, the objectives for the Phase 1-2a trial are: to establish the safety of administration of INGAP to humans, and secondly, to seek trends toward efficacy.
Kathy F.
Dr. Vinik, how long are the Phase1-2a trials expected to last? When is the next phase of trials expected to begin? And will aternative locations be selected for the additional phases?
Dr. Vinik
The Phase 1-2a trials should be done before summer of 2002.
Donna
What is the process to submit a patient information form for selecting candidates? Will there be a study on islet transplant and INGAP at the same time?
Dr. Vinik
The process to submit patient information is to contact the GMP coordinating center for the study, namely gmpcompanies.com.
Patrice
Would being on a beta cell transplant waiting list disqualify one from being part of your studies?
Dr. Vinik
Being on a beta cell transplant list does not preclude you from participation if you meet the entry criteria for the study.
Cheri
Could you tell us what the entry criteria for the study will be? Will you accept participants with complications? Kidney problems? Neuropathy? Retinopathy?
Kristina
Please let us know what the inclusion criteria are (e.g. age range), how INGAP is being administered and for how long you plan to give the agent. Thanks.
Dr. Vinik
Kristina, please get that information from gmpcompanies.com.
Natasha
Dr. Vinik, I have just been to gmpcompanies.com, and it says on the website that these places where the trials are going on are just recruiting from their own geographical location. Does this mean that I cannot apply for my mother?
Gwen
I live in Shreveport, Louisiana, and we have large medical centers and research facilities. I want to know when we can participate. I called San Antonio and was told that they want participants in the local area for now.
Dr. Vinik
I think that is true. If you want to learn more details you can contact gmpcompanies.com.
I cannot answer for trial selection sites since this is not in my purview. We are trying to make this as objective as possible, and for this reason, I do not participate in that decision-making.
Heidyn
Dr. Vinik, are all your trial sites full?
Dr. Vinik
Heidyn, the trials are not full at this stage because they are being done in modules.
Kathy F.
I contacted GMP Companies last Friday and was told that all the slots for Type 1 have been filled, but they are still looking for Type 2 participants.
JP
Hi Dr. Vinik, thank you for all the work you are doing for us. Can you tell me when there will be a clinical trial in Canada?
John
Dr. Vinik, can you tell us all the research locations?
Deb
Here is a link to the GMP Companies website:
http://www.gmpcompanies.com/html/core/index.html
Shana
Dr. Vinik, in your trials, were the animals you used autoimmune?
Dr. Vinik
Yes, the animals in our studies did have autoimmune disease and after treatment with INGAP, the islets seemed to have less autoimmune reaction within the pancreas. This, of course, does not guarantee that it will be the same in humans, but it is salutary.
Alan F. Bachrach, M.D.
Dr. Vinik, thanks for coming to “talk” to us again. Are the human trials being done on Type 1 diabetics? What are the dependent variables? Will peptide C or some other indicator of native insulin production be measured in these trials? Thanks, Alan.
Dr. Vinik
The measurements being made include all the normal safety data, for example, blood pressure, pulse rate and biochemical indices of liver and kidney function and the like. Additional measures include blood glucose levels, insulin dosage and production of C-peptide.
Cheri
Dr. Vinik, welcome. My question is that as far as I understand, it is not yet known if immune suppressants will be needed. Is that correct?
Dr. Vinik
Cheri, you are correct. We do not know if immunosuppressives will be needed for the Type 1 diabetes patients.
Judie
Has INGAP received widespread support in the medical community? Why, or why not?
Dr. Vinik
The community has been incredibly supportive, especially the Diabetes Institutes Foundation with its supporters in Norfolk, Tidewater area, Virginia Beach and New York as well as elsewhere.
Heidyn
Dr. Vinik, what would be done if participants developed hyperinsinoma (produced too much insulin)?
Mary
Did any of the animals in the study suffer from hypoglycemia when injected with INGAP?
Ellen
Dr. Vinik, do you feel that you can inject this substance into a person with Type 1 autoimmune diabetes, and that person will be able to regenerate islets and those islets won’t be attacked by the same system that originally destroyed the islets in the body? How do you check that there won’t be an overproduction of the islets?
Diane
I would also like to know about the possibility of the overproduction of islet cells and the danger of producing too much insulin.
Tim
If the islets are glucose sensitive, it wouldn’t matter if there was overproduction ofislets, would it Dr. Vinik?
Dr. Vinik
The question of overproduction of insulin does not seem to be a concern. Fascinatingly, when we gave INGAP to normal animals, they developed an increase in their beta cell mass in the pancreas, but did not oversecrete insulin and never became hypoglycemic. We demonstrated that the new islet cells behaved quite responsibly and only secreted insulin when it was needed and not in excess. Furthermore, the islets grew in number to a certain compliment and then were restrained by factors in the pancreas. That is to say the new organ of Langerhans is a very mature and dependable organ.
Martha
Would chances be better for islet cell regeneration if you became diabetic later in life, say late 20’s, than it would be for someone that became diabetic at an early age?
Dr. Vinik
The chances of responding might not depend on when the diabetes started. For example, we have studied the pancreases of patients over the age of 60 and found the precursor adult stem cells resident in the pancreas. We have also shown that INGAP is expressed in these pancreases so this augurs well for the person with long-standing diabetes.
Exgon
Dr. Vinik, are human trials going on involving BOTH the entire INGAP protein as well as the “active” 15 residue peptide?
Dr. Vinik
The current trials are only on INGAP Peptide. When we established that the Peptide was just as effective if not more so that the whole protein, we went ahead with developing the Peptide for human trials. Of course, the fact that the Peptide can be synthesized chemically not requiring recombinant techniques makes it more likely that we have a pure compound free of any of the contaminants found in the recombinant full lenth protein.
Judie
Do you think INGAP would be a better or satisfactory alternative to what stem cell research might accomplish?
Dr. Vinik
Judie, INGAP is a means of stimulating adult stem cells in your own body. That at least eliminates one of the problems of foreign stem cells.
MAR
Dr. Vinik, I first heard of your research in an article in the Virginian-Pilot just after my daughter was diagnosed January 23, 1997. The article predicted “a cure in five years.” I hoped then as I hope now. You’re pretty much on schedule. Thank you for hanging in there for us.
Dr. Vinik
Thanks for having faith, and I think we are ahead of the schedule I had anticipated thanks to the incredible support of our Foundation and GMP.
Linda
Dr. Vinik, Hi…I have been following your research since my daughter went down to the Strelitz Diabetes Institutes in Norfolk, VA at age 3 (9 years ago). Can you give us a ballpark answer as to when this might become available to the diabetic public at large? Also, as a financial supporter of your research, can you let others in on this chat know how to help? Thanks for all your work.
Kathy
Dr. Vinik, I think we are all so excited about how rapidly the research has progressed on INGAP! Can you give us any idea of when it is hoped or believed that this might be available to the diabetic population at large?
Shana
If everything went well with these studies, how long do you think it would be before INGAP became available to the general public, Dr. Vinik?
Martin
Scott Mohrland of GMP said “The drug could be on the market within 10 years.” Is there any hope it would be sooner?
Dr. Vinik
Martin, I think Scott is being misquoted. Within 10 years can be much sooner. We will, of course, urge all haste.
Ellen
Dr. Vinik, could you please describe how INGAP works and how the autoimmune process will not destroy the ability of the islets to regenerate and function?
Lyn
Dr. Vinik, Dr. Furstman’s findings show that “Training” what caused the disease in the first place, stops the attack on new cells…..wouldn’t this be a major step in the INGAP?
Dr. Vinik
Lyn, any approach to stop or abate the process that initiated the assault on the pancreas will be helpful. We are clearly considering all avenues to cater for the contingency that the newly formed islets would be subject to the same assault that their parent islets suffered by the autoimmune and destructive forces operative in the beginning. There have been a number of advances in this arena which add hope to our approach.
Judy
Dr. Vinik, what’s the next step in your research and how many steps must you complete before this might be ready for the general population? Thank you so much for this research!
Majorie
Dr. Vinik, the advantages of this treatment seem immense at this point. What do you foresee as the hurdles facing your research in the near future?
Dr. Vinik
There are several obstacles to overcome. For example, finding out what the optimum dose, the frequency and what we can do to combat any residual autoimmunity are amongst those most important.
Mary
After the animals were injected with INGAP, how much time passed before the second injection was needed.
Dr. Vinik
Mary, we gave the animals repeated doses for up to 40 days. The response was obvious in 10 days and persisted for 10 days after we stopped the injections. We need to learn the responses in humans, and this is where the studies will go.
Kathy F.
Yes, how much time, on average, is needed for islet cell regeneration to be stimulated and for a response to be noted? How do you deal with taking exogenous insulin if you are producing your own?!!!! Do you stop having hypo rxns when these cells are produced, despite the injection of insulin, because the cells are behaving as they should and responding to blood sugar drops?
Dr. Vinik
Kathy, those are all pertinent questions. The reason we have designed the clinical studies so carefully is for us to learn if we can achieve lower glucose levels, reduce the insulin dose or increase endogenous insulin production. This is all being very carefully monitored and titrated so that, hopefully, any one ore more of these events will indicate a trend in the right direction.
Lisa
Many diabetics are skinny. If INGAP is successful, will it change so that skinny diabetics can also be cured?
Dr. Vinik
Skinny diabetics may have a better chance of responding since the new islets do not have to contend with any resistance to the action of insulin. On the other hand, skinny people with diabetes may have more autoimunity and would then tend to destroy their islets more frequently than overweight Type 2 diabetics. We will have to see. Both populations are included in the trials.
Lisa
Underweight diabetics are not included.
Dr. Vinik
Skinny type 2’s are needed for the trials.
Lisa
But underweight Type 1’s are not allowed to participate. I hope that will change!
Kathy F
What about BEYOND 10 days after INGAP injections were stopped? Are the islets still viable?
Natasha
I second Kathy’s question.
Jim
I second Kathy’s question. Will the INGAP injections be ongoing like insulin is now, or will it be used for only a period of time and then the body will “take over” the process of regenerating new cells as needed?
Tom Gleeson
Dr. Vinik, I’m curious about the mechanism of regeneration. Does it continue for a short or long period of time? How often would the injections of INGAP be necessary to keep pace with the immunosuppression issues?
Dr. Vinik
We are doing the studies on the robustness of the new islets and their resilience to further assault. Hope to have those results at our next chat.
Carolyn
I apologize if this question has been asked. I am signing in very late. I have heard that one of the things that INGAP must overcome is the autoimmune process that destroys islets. After 20 years of insulin therapy, I recently had a c-peptide test that showed that I am producing half the amount of insulin that a normal person does. What would prevent total destruction of the islets by the autoimmune process?
Dr. Vinik
Carolyn, it is fascinating that some people develop a latent autoimmune diabetes of adults and can have a low grade autoimmune response that does not annihilate the islets but destroys them slowly so that even years later there are residual islets.
Majorie
Dr. Vinik, we cannot adequately express our gratitude for your tireless efforts and the promise it offers for us and our children. We thank you for the time you have spent tonight and your willingness to follow-up some of these questions. The excitement in the room has been overwhelming.
Dr. Vinik
Happy to have joined you for the chat. Take Care. AIV
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