Linking Diabetics Coast 2 Coast
Dr. Antonello Pileggi, M.D., Ph.D. of the Diabetes Research Institute June 18, 2008
*** (16:59):Welcome to Dr. Pileggi of DRI chat , Dr. Pileggi !
Dr. Pileggi says to (17:00):hi everyone!
sugarchallenged says to (17:00):hello Dr
bella says to (17:00):hey doc:)
gina says to (17:00):Hi Dr. P
oopsy says to (17:00):hi dr and mh
sugarchallenged says to (17:00)::D
PhillyGuy says to (17:00):Good Evening Dr
JIMBOB48 says to (17:00):HI THERE
AllieB2 says to (17:00):good evening everybody!
oopsy says to (17:00):hi allie
gina says to (17:01):HEY EVERYONE JUST A REMINDER GIVE DR. PILEGGI A CHANCE TO ANSWER BETWEEN QUESTIONS
SO HE ISNT OVERWHELMED
sstrumello says to (17:01):Hello Everyone!
oopsy says to (17:01):hi
gina says to (17:01):Dr. Pileggi would you like to give us an overview of your work?
Dr. Pileggi says to (17:02):I'll try
gina says to (17:02):for the people that don't know what you are doing.
gina says to (17:02):well not familiar i mean
avanessa22 says to (17:02):Dr. Pileggi I was fortune enough to visit the DRI center three years ago and got to attend a MYD workshop. Are they still having those.
Dr. Pileggi says to (17:03):Yes, Dr. Meneghini is very active with that program
avanessa22 says to (17:03):Great, because I tell people all the time about that program, It changed my life
sugarchallenged says to (17:04):how?
Dr. Pileggi says to (17:04):I have been working at the DRI for the last 10 years mostly in translational research related to islet cell transplantation, and also in part working with the Clinical Islet Transplant Team.
avanessa22 says to (17:04):I learned more in a few days about diabetes than I did in the 20 years that I had it
Dr. Pileggi says to (17:05):Most of the research I am involved in is focused on improving the outcome of beta cell replacement
Dr. Pileggi says to (17:06):they are trying to overcome the current limitations emerging from clinical trials of islet transplantation by going back in the lab and experimenting novel approaches that could make a difference
avanessa22 says to (17:07):what are some of the current limitations?
Dr. Pileggi says to (17:07):there are two major themes that are key in this field, limitation of islet source and need for life long immuno-suppression
AllieB2 says to (17:08):how successful has the 'oxygen sandwich' approach been for islet cell survival?
AllieB2 says to (17:08):or seaweed / kelp encapsulatoin?
AllieB2 says to (17:08):encapsulation
gina says to (17:09):that was the research bernie tuch was doing right
gina says to (17:09):the seaweed
AllieB2 says to (17:10):i though it didn't evoke the autoimmune response...or at least not as aggressively as raw islets
Dr. Pileggi says to (17:10):there are promising emerging technologies that have been tested. The Oxygen Sandwich is showing improved maturation of beta cells from stem cells in vitro. we are currently testing it also for islets in culture to enhance their viability
Dr. Pileggi says to (17:11):there are several encapsulation strategies that may be of assistance in improving islet cell survival without the need for chronic, high doses immunosuppression
sstrumello says to (17:11):Dr. P., can you comment on the June 2008 issue of the American Journal of Transplantation featured the results of an improvement made to the traditional "Edmonton Protocol" implemented by the University of Illinois at Chicago (UIC)?
Dr. Pileggi says to (17:13):This is an interesting and very promising approach, that is to include in the treatment also exenatide. the results are very promising as they could improve function with lower islet numbers
sstrumello says to (17:14):exenatide being better known as Byetta, the type 2 medicine
Dr. Pileggi says to (17:14):we have similar observations at DRI and believe this strategy may be of assistance in reducing the islet requirements to attain sustained function after islet transplantation
Dr. Pileggi says to (17:14):the drug (byetta) has protective properties for islet cells, and also improved beta-cell function
AllieB2 says to (17:16):Dr. Pileggi -- since it was found that stem cells can derive from skin cells.... and the skin from the scrotum is non-comedogenic -- has DRI looked into culturing beta cells from the human scrotum dermis? sertoli is it?
Dr. Pileggi says to (17:16):of course this is not the only magic bullet, we need to implement a sequential, integrated approach to combine other important changes in the therapeutic regimen to improve the function of transplanted islets and have insulin-independence long-term
AllieB2 says to (17:17):(not sure if "non-comedogenic" is the right word...but won't evoke the same type of autoimmune reaction)
Dr. Pileggi says to (17:18):the Sertoli Cells are inside the testis, the scrotum is the skin around them. the properties known for Sertoli cells are related to immunoprotection. Stem cells are now isolated from a variety of adult tissues and it may be possible to induce them to dif
Dr. Pileggi says to (17:19): differentiate into beta cells under appropriate conditions. this is the most challenging part of the story
AllieB2 says to (17:19):but would using them in cultivating new beta cells aid in reducing the need for immunosuppression once the new beta cells are implanted?
Dr. Pileggi says to (17:20):there are experimental conditions in which Sertoli cells can improve the survival of islet cells in animals. In humans, there has not been proven
advantages so far
Dr. Pileggi says to (17:21):the sertoli cells are being studied to try and reproduce the immuno provilege properties of the testis.
Dr. Pileggi says to (17:22):other cells, such as mesenchymal stem cells (MSCs) are also being studied for their interesting immunoprotective and tissue repair properties
AllieB2 says to (17:22):that's really fascinating
AllieB2 says to (17:23):perhaps there's a counter cell (from the female) that is needed to complete "unlocking" the equation?
Dr. Pileggi says to (17:23):LOL
AllieB2 says to (17:23):;)
Dr. Pileggi says to (17:23):I'll bring this tissue o the lab meeting tomorrow
sstrumello says to (17:24):Dr. P., the FDA currently has proposed guidelines now awaiting comment which could impact islet transplantation ... have you reviewed those guidelines, and is there anything that might be appropriate to change?
Dr. Pileggi says to (17:24):Interestingly, during pregnancy there is a lot going on to 'tolerate' the fetus.
AllieB2 says to (17:25):i've heard diabetes is mitigated by pregnancy -- haven't tested the theory though
Dr. Pileggi says to (17:25):it is interesting that MSC can be obtained from a number of tissues of adult and embryonic, so there is the possibility of dealing with beta cell
regeneration and immunity with the same unlimited source
sstrumello says to (17:26):Notably, the FDA guidance suggests stimulated c-peptide of <0.7 -- mine is less than that and I've had type 1 for more than 32 years
sstrumello says to (17:26):I mean mine is greater than that ... rendering me ineligible
Listersmate says to (17:27):Hi. I'm Tony.
Dr. Pileggi says to (17:27):we enroll patients with T1DM with undetectable c-peptide for our trials. this is due to the fact that it is the only way we can monitor the islets transplanted as they will be the only source for c-peptide afterwards
sstrumello says to (17:28):But should the FDA be defining that is a cutoff?
Dr. Pileggi says to (17:29):I have not gone in depth into the recent FDA doc, but the
guidelines are generally drafted based on the current clinical standards
sstrumello says to (17:29):Comments on the FDA guidance are due August 20, 2008
AllieB2 says to (17:30):Scott - sometimes I wonder if animal insulin offered lipophilic protection that slowed or stopped the growth\ of the autoimmune destruction of beta cells. That's my theory and I'm sticking to it ;)
Dr. Pileggi says to (17:30):I promise, I will get informed on time
sstrumello says to (17:30):Thanks, Dr. P.!
sstrumello says to AllieB2 (17:31):Perhaps, Allie!
Dr. Pileggi says to (17:32): encapsulation then: the seaweed trial seems interesting, and we are looking forward to hearing the preliminary clinical results shortly
Dr. Pileggi says to (17:32):there have been ups and downs with encapsulation in the past
oopsy says to (17:32):Allie, how did you come up with that theory?
AllieB2 says to (17:33):1) Honeymoon periods, nowadays, are nearly non-existant
AllieB2 says to (17:33):2) diabetics who were initially started on animal insulin still can stimulate C-peptide
oopsy says to (17:33):hayley never had a honeymoon
Dr. Pileggi says to (17:33):There is emerging technology of nanocoating the islets that may lead to immunoisolation without the problems of poos oxygen diffusion of micro capsules
AllieB2 says to (17:34):3) all insulin analogues are cultiaveted in yeast or e.Coli -- which (more of less) vaccinate the body from insulin
AllieB2 says to (17:34):(sorry -- I'll stick to the topic we're discussing)
sstrumello says to (17:34):Is there anything being tried to extend the life of transplanted islets? The period of insulin-independence is still fairly limited, and I'm curious what researchers are looking at to improve that!
oopsy says to (17:34):thanks...just wondering
Dr. Pileggi says to (17:35):we are recognizing that multiple factors may concur to the observed limited insulin independence of recent clinical trials with the Edmonton Protocol
Dr. Pileggi says to (17:36):there is increasing evidence that some of the drugs are beta-cell toxic, and that they may hinder the self renewal of beta cells over time
Dr. Pileggi says to (17:37):at our center, we started modifying the immunosuppressive protocol to explore drugs with lower diabetogenic potential, and possibly better immunosuppressive properties
Dr. Pileggi says to (17:38):the initial results of the use of a new lymphodepleting agent (Capath-1H) are quite remarkable
Dr. Pileggi says to (17:39):also, the inclusion of glucagone-like peptide-1 analogs (i.e., Byetta) has also shown excellent results in prolonging graft function
sstrumello says to (17:39):Hmmm, what about the transplant location in the liver? Is that an issue, too?
Dr. Pileggi says to (17:40):right, the levels of toxins in the liver may also contribute to the dysfunction, and to the loss of a substantial islet number soon after transplantation
Dr. Pileggi says to (17:40):we are working on the development of alternative sites for islets
Dr. Pileggi says to (17:41):Dr. Kenyon is studying the possibility of transplanting islets into the omentum (an anatomical structure in the abdomen) with new scaffolds
Dr. Pileggi says to (17:42):There is an interdisciplinary team working on a biohybrid device concept that may allow implantation of the islets under the skin in a prevascularized site
AllieB2 says to (17:42):Dr. Pileggi -- where in the body is TNF-alpha made?
AllieB2 says to (17:42):...I'm asking because maybe those are the cells that are weak in a Type 1 body....
AllieB2 says to (17:43):and if they are "replaced" or "repaired".... that might assist in beta cell regeneration -- like Dr. Faustman's BCG treatment
Dr. Pileggi says to (17:43):TNF-alpha is produced by several of the cells of the immune system (maily macrophages) in most tissues
gina says to (17:43):Dr. Faustman i still need to get her in a chat here!
gina says to (17:44):Dr. P maybe allie can work with you lol
AllieB2 says to (17:44):LOL -- one of my friends calls me "counter-productive" because I think about *d* so much LoL
AllieB2 says to (17:45):I'm no good at this "work" thing -- I like brainstorming
gina says to (17:45):amen sista
Dr. Pileggi says to (17:45):TNF-alpha is produced in inflammation and infections to boost the immune response. we consider it a bad cytokine for islets (it kills them) and in clinical trials we use anti-TNF-a to enhance islet engraftment
Dr. Pileggi says to (17:45):we always welcome volunteers in our lab
AllieB2 says to (17:46):what if you didn't have to engraft the islets, in the first place?
AllieB2 says to (17:46):TNF-alpha, first... islets naturally grow?
Dr. Pileggi says to (17:47):well, sorry for the miscommunication... we refer to engraftment as the process of survival and adaptation of islets to the new implantation site
AllieB2 says to (17:48):my fault -- I'm terrible at communication
Dr. Pileggi says to (17:48):which is a prerequirement for islets to being able to do their job
Dr. Pileggi says to (17:48):TNF-a blockade helps reducing inflammation and promote islet cell survival
Dr. Pileggi says to (17:49):please, allow me to stress that we have probably overemphasized in the past the relevance of insulin independence after islet transplantation. We have seen that improved metabolic control and prevention of severe hypoglycemia can be achieved after
Dr. Pileggi says to (17:51):islet transplant, even if insulin is needed to attain good metabolic control. this is a remarkable result, particularly in the patients with brittle diabetes that receive the transplant because of the hypo unawareness and frequent severe lows
Dr. Pileggi says to (17:51):some of the patients who lost 'insulin independence' by 5 years in the Edmonton-like trial had excellent control with minimal insulin at that time
AllieB2 says to (17:52): definitely the biggest dangers of diabetes -- life threatening...especially in light of the new "low thresholds" getting lower
Dr. Pileggi says to (17:53):right, we are making continuous progress and our goals are getting more ambitious. however, we are really learning a lot from one trial to another, and there is always a gain for the better
Dr. Pileggi says to (17:54):we are working for a cure, and we need to get into intermediate steps
Dr. Pileggi says to (17:54):that will lead us eventually there
AllieB2 says to (17:55):what about transplanting alpha cells?
AllieB2 says to (17:55):bear with me a second....
Dr. Pileggi says to (17:56):We are very excited about the biohybrid device studies because we are trying to create an immunoprivilege site into a bioartificial endocrine pancreas
sstrumello says to (17:57):very interesting!
Dr. Pileggi says to (17:57):when we transplant islets, we are implanting all cell subsets contained in each cluster. there are good numbers of alpha and beta cells in each islet
Dr. Pileggi says to (17:58):this may be one of the reasons that after islet transplantation there is a reduction of severe hypos, and somehow some restoration of prodromic symptoms
Dr. Pileggi says to (18:00):the good function of each of the cells in the islets may require that alha, beta, delta cells are in contact and talk to each other
Dr. Pileggi says to (18:00):that is probably why alpha cells, that are spared from the autoimmune process, are unable to do their job in T1DM
AllieB2 says to (18:01):DELTA :)
Dr. Pileggi says to (18:01):but it is true also for the beta cells
Dr. Pileggi says to (18:01):Delta = somatostatin secreting cells
Dr. Pileggi says to (18:01):it is to show off my knowlede of greek alphabet
gina says to (18:01):haha
PhillyGuy says to (18:02):lol
sstrumello says to (18:02):LOL
AllieB2 says to (18:02):that would be an interesting treatment (from the vial)....
somatostatin
AllieB2 says to (18:02):wake up *perfect*...
AllieB2 says to (18:02):stay perfect... all day
Dr. Pileggi says to (18:03):all right, time is up! Has been a great pleasure chatting with such an active crew
AllieB2 says to (18:04):Thank you so much, Dr. Pileggi!!
jon says (18:04):Thanks for chatting with us!
oopsy says to (18:04):thanks dr
tmana says to (18:04):Definitely... thanks :)
jon says (18:04):Thanks everybody for coming!
JIMBOB48 says to (18:04):THANKS DOC
sstrumello says to (18:04):thanks!!
Dr. Pileggi says to (18:04):talk to you soon. All the best
jon says (18:04):We will post a transcript tonight.
Dr. Pileggi says to (18:04):...ciao...
PhillyGuy says to (18:04):Thanks All
gina says to (18:04):thanks everyone
Dr. Pileggi says to (17:00):hi everyone!
sugarchallenged says to (17:00):hello Dr
bella says to (17:00):hey doc:)
gina says to (17:00):Hi Dr. P
oopsy says to (17:00):hi dr and mh
sugarchallenged says to (17:00)::D
PhillyGuy says to (17:00):Good Evening Dr
JIMBOB48 says to (17:00):HI THERE
AllieB2 says to (17:00):good evening everybody!
oopsy says to (17:00):hi allie
gina says to (17:01):HEY EVERYONE JUST A REMINDER GIVE DR. PILEGGI A CHANCE TO ANSWER BETWEEN QUESTIONS
SO HE ISNT OVERWHELMED
sstrumello says to (17:01):Hello Everyone!
oopsy says to (17:01):hi
gina says to (17:01):Dr. Pileggi would you like to give us an overview of your work?
Dr. Pileggi says to (17:02):I'll try
gina says to (17:02):for the people that don't know what you are doing.
gina says to (17:02):well not familiar i mean
avanessa22 says to (17:02):Dr. Pileggi I was fortune enough to visit the DRI center three years ago and got to attend a MYD workshop. Are they still having those.
Dr. Pileggi says to (17:03):Yes, Dr. Meneghini is very active with that program
avanessa22 says to (17:03):Great, because I tell people all the time about that program, It changed my life
sugarchallenged says to (17:04):how?
Dr. Pileggi says to (17:04):I have been working at the DRI for the last 10 years mostly in translational research related to islet cell transplantation, and also in part working with the Clinical Islet Transplant Team.
avanessa22 says to (17:04):I learned more in a few days about diabetes than I did in the 20 years that I had it
Dr. Pileggi says to (17:05):Most of the research I am involved in is focused on improving the outcome of beta cell replacement
Dr. Pileggi says to (17:06):they are trying to overcome the current limitations emerging from clinical trials of islet transplantation by going back in the lab and experimenting novel approaches that could make a difference
avanessa22 says to (17:07):what are some of the current limitations?
Dr. Pileggi says to (17:07):there are two major themes that are key in this field, limitation of islet source and need for life long immuno-suppression
AllieB2 says to (17:08):how successful has the 'oxygen sandwich' approach been for islet cell survival?
AllieB2 says to (17:08):or seaweed / kelp encapsulatoin?
AllieB2 says to (17:08):encapsulation
gina says to (17:09):that was the research bernie tuch was doing right
gina says to (17:09):the seaweed
AllieB2 says to (17:10):i though it didn't evoke the autoimmune response...or at least not as aggressively as raw islets
Dr. Pileggi says to (17:10):there are promising emerging technologies that have been tested. The Oxygen Sandwich is showing improved maturation of beta cells from stem cells in vitro. we are currently testing it also for islets in culture to enhance their viability
Dr. Pileggi says to (17:11):there are several encapsulation strategies that may be of assistance in improving islet cell survival without the need for chronic, high doses immunosuppression
sstrumello says to (17:11):Dr. P., can you comment on the June 2008 issue of the American Journal of Transplantation featured the results of an improvement made to the traditional "Edmonton Protocol" implemented by the University of Illinois at Chicago (UIC)?
Dr. Pileggi says to (17:13):This is an interesting and very promising approach, that is to include in the treatment also exenatide. the results are very promising as they could improve function with lower islet numbers
sstrumello says to (17:14):exenatide being better known as Byetta, the type 2 medicine
Dr. Pileggi says to (17:14):we have similar observations at DRI and believe this strategy may be of assistance in reducing the islet requirements to attain sustained function after islet transplantation
Dr. Pileggi says to (17:14):the drug (byetta) has protective properties for islet cells, and also improved beta-cell function
AllieB2 says to (17:16):Dr. Pileggi -- since it was found that stem cells can derive from skin cells.... and the skin from the scrotum is non-comedogenic -- has DRI looked into culturing beta cells from the human scrotum dermis? sertoli is it?
Dr. Pileggi says to (17:16):of course this is not the only magic bullet, we need to implement a sequential, integrated approach to combine other important changes in the therapeutic regimen to improve the function of transplanted islets and have insulin-independence long-term
AllieB2 says to (17:17):(not sure if "non-comedogenic" is the right word...but won't evoke the same type of autoimmune reaction)
Dr. Pileggi says to (17:18):the Sertoli Cells are inside the testis, the scrotum is the skin around them. the properties known for Sertoli cells are related to immunoprotection. Stem cells are now isolated from a variety of adult tissues and it may be possible to induce them to dif
Dr. Pileggi says to (17:19): differentiate into beta cells under appropriate conditions. this is the most challenging part of the story
AllieB2 says to (17:19):but would using them in cultivating new beta cells aid in reducing the need for immunosuppression once the new beta cells are implanted?
Dr. Pileggi says to (17:20):there are experimental conditions in which Sertoli cells can improve the survival of islet cells in animals. In humans, there has not been proven
advantages so far
Dr. Pileggi says to (17:21):the sertoli cells are being studied to try and reproduce the immuno provilege properties of the testis.
Dr. Pileggi says to (17:22):other cells, such as mesenchymal stem cells (MSCs) are also being studied for their interesting immunoprotective and tissue repair properties
AllieB2 says to (17:22):that's really fascinating
AllieB2 says to (17:23):perhaps there's a counter cell (from the female) that is needed to complete "unlocking" the equation?
Dr. Pileggi says to (17:23):LOL
AllieB2 says to (17:23):;)
Dr. Pileggi says to (17:23):I'll bring this tissue o the lab meeting tomorrow
sstrumello says to (17:24):Dr. P., the FDA currently has proposed guidelines now awaiting comment which could impact islet transplantation ... have you reviewed those guidelines, and is there anything that might be appropriate to change?
Dr. Pileggi says to (17:24):Interestingly, during pregnancy there is a lot going on to 'tolerate' the fetus.
AllieB2 says to (17:25):i've heard diabetes is mitigated by pregnancy -- haven't tested the theory though
Dr. Pileggi says to (17:25):it is interesting that MSC can be obtained from a number of tissues of adult and embryonic, so there is the possibility of dealing with beta cell
regeneration and immunity with the same unlimited source
sstrumello says to (17:26):Notably, the FDA guidance suggests stimulated c-peptide of <0.7 -- mine is less than that and I've had type 1 for more than 32 years
sstrumello says to (17:26):I mean mine is greater than that ... rendering me ineligible
Listersmate says to (17:27):Hi. I'm Tony.
Dr. Pileggi says to (17:27):we enroll patients with T1DM with undetectable c-peptide for our trials. this is due to the fact that it is the only way we can monitor the islets transplanted as they will be the only source for c-peptide afterwards
sstrumello says to (17:28):But should the FDA be defining that is a cutoff?
Dr. Pileggi says to (17:29):I have not gone in depth into the recent FDA doc, but the
guidelines are generally drafted based on the current clinical standards
sstrumello says to (17:29):Comments on the FDA guidance are due August 20, 2008
AllieB2 says to (17:30):Scott - sometimes I wonder if animal insulin offered lipophilic protection that slowed or stopped the growth\ of the autoimmune destruction of beta cells. That's my theory and I'm sticking to it ;)
Dr. Pileggi says to (17:30):I promise, I will get informed on time
sstrumello says to (17:30):Thanks, Dr. P.!
sstrumello says to AllieB2 (17:31):Perhaps, Allie!
Dr. Pileggi says to (17:32): encapsulation then: the seaweed trial seems interesting, and we are looking forward to hearing the preliminary clinical results shortly
Dr. Pileggi says to (17:32):there have been ups and downs with encapsulation in the past
oopsy says to (17:32):Allie, how did you come up with that theory?
AllieB2 says to (17:33):1) Honeymoon periods, nowadays, are nearly non-existant
AllieB2 says to (17:33):2) diabetics who were initially started on animal insulin still can stimulate C-peptide
oopsy says to (17:33):hayley never had a honeymoon
Dr. Pileggi says to (17:33):There is emerging technology of nanocoating the islets that may lead to immunoisolation without the problems of poos oxygen diffusion of micro capsules
AllieB2 says to (17:34):3) all insulin analogues are cultiaveted in yeast or e.Coli -- which (more of less) vaccinate the body from insulin
AllieB2 says to (17:34):(sorry -- I'll stick to the topic we're discussing)
sstrumello says to (17:34):Is there anything being tried to extend the life of transplanted islets? The period of insulin-independence is still fairly limited, and I'm curious what researchers are looking at to improve that!
oopsy says to (17:34):thanks...just wondering
Dr. Pileggi says to (17:35):we are recognizing that multiple factors may concur to the observed limited insulin independence of recent clinical trials with the Edmonton Protocol
Dr. Pileggi says to (17:36):there is increasing evidence that some of the drugs are beta-cell toxic, and that they may hinder the self renewal of beta cells over time
Dr. Pileggi says to (17:37):at our center, we started modifying the immunosuppressive protocol to explore drugs with lower diabetogenic potential, and possibly better immunosuppressive properties
Dr. Pileggi says to (17:38):the initial results of the use of a new lymphodepleting agent (Capath-1H) are quite remarkable
Dr. Pileggi says to (17:39):also, the inclusion of glucagone-like peptide-1 analogs (i.e., Byetta) has also shown excellent results in prolonging graft function
sstrumello says to (17:39):Hmmm, what about the transplant location in the liver? Is that an issue, too?
Dr. Pileggi says to (17:40):right, the levels of toxins in the liver may also contribute to the dysfunction, and to the loss of a substantial islet number soon after transplantation
Dr. Pileggi says to (17:40):we are working on the development of alternative sites for islets
Dr. Pileggi says to (17:41):Dr. Kenyon is studying the possibility of transplanting islets into the omentum (an anatomical structure in the abdomen) with new scaffolds
Dr. Pileggi says to (17:42):There is an interdisciplinary team working on a biohybrid device concept that may allow implantation of the islets under the skin in a prevascularized site
AllieB2 says to (17:42):Dr. Pileggi -- where in the body is TNF-alpha made?
AllieB2 says to (17:42):...I'm asking because maybe those are the cells that are weak in a Type 1 body....
AllieB2 says to (17:43):and if they are "replaced" or "repaired".... that might assist in beta cell regeneration -- like Dr. Faustman's BCG treatment
Dr. Pileggi says to (17:43):TNF-alpha is produced by several of the cells of the immune system (maily macrophages) in most tissues
gina says to (17:43):Dr. Faustman i still need to get her in a chat here!
gina says to (17:44):Dr. P maybe allie can work with you lol
AllieB2 says to (17:44):LOL -- one of my friends calls me "counter-productive" because I think about *d* so much LoL
AllieB2 says to (17:45):I'm no good at this "work" thing -- I like brainstorming
gina says to (17:45):amen sista
Dr. Pileggi says to (17:45):TNF-alpha is produced in inflammation and infections to boost the immune response. we consider it a bad cytokine for islets (it kills them) and in clinical trials we use anti-TNF-a to enhance islet engraftment
Dr. Pileggi says to (17:45):we always welcome volunteers in our lab
AllieB2 says to (17:46):what if you didn't have to engraft the islets, in the first place?
AllieB2 says to (17:46):TNF-alpha, first... islets naturally grow?
Dr. Pileggi says to (17:47):well, sorry for the miscommunication... we refer to engraftment as the process of survival and adaptation of islets to the new implantation site
AllieB2 says to (17:48):my fault -- I'm terrible at communication
Dr. Pileggi says to (17:48):which is a prerequirement for islets to being able to do their job
Dr. Pileggi says to (17:48):TNF-a blockade helps reducing inflammation and promote islet cell survival
Dr. Pileggi says to (17:49):please, allow me to stress that we have probably overemphasized in the past the relevance of insulin independence after islet transplantation. We have seen that improved metabolic control and prevention of severe hypoglycemia can be achieved after
Dr. Pileggi says to (17:51):islet transplant, even if insulin is needed to attain good metabolic control. this is a remarkable result, particularly in the patients with brittle diabetes that receive the transplant because of the hypo unawareness and frequent severe lows
Dr. Pileggi says to (17:51):some of the patients who lost 'insulin independence' by 5 years in the Edmonton-like trial had excellent control with minimal insulin at that time
AllieB2 says to (17:52): definitely the biggest dangers of diabetes -- life threatening...especially in light of the new "low thresholds" getting lower
Dr. Pileggi says to (17:53):right, we are making continuous progress and our goals are getting more ambitious. however, we are really learning a lot from one trial to another, and there is always a gain for the better
Dr. Pileggi says to (17:54):we are working for a cure, and we need to get into intermediate steps
Dr. Pileggi says to (17:54):that will lead us eventually there
AllieB2 says to (17:55):what about transplanting alpha cells?
AllieB2 says to (17:55):bear with me a second....
Dr. Pileggi says to (17:56):We are very excited about the biohybrid device studies because we are trying to create an immunoprivilege site into a bioartificial endocrine pancreas
sstrumello says to (17:57):very interesting!
Dr. Pileggi says to (17:57):when we transplant islets, we are implanting all cell subsets contained in each cluster. there are good numbers of alpha and beta cells in each islet
Dr. Pileggi says to (17:58):this may be one of the reasons that after islet transplantation there is a reduction of severe hypos, and somehow some restoration of prodromic symptoms
Dr. Pileggi says to (18:00):the good function of each of the cells in the islets may require that alha, beta, delta cells are in contact and talk to each other
Dr. Pileggi says to (18:00):that is probably why alpha cells, that are spared from the autoimmune process, are unable to do their job in T1DM
AllieB2 says to (18:01):DELTA :)
Dr. Pileggi says to (18:01):but it is true also for the beta cells
Dr. Pileggi says to (18:01):Delta = somatostatin secreting cells
Dr. Pileggi says to (18:01):it is to show off my knowlede of greek alphabet
gina says to (18:01):haha
PhillyGuy says to (18:02):lol
sstrumello says to (18:02):LOL
AllieB2 says to (18:02):that would be an interesting treatment (from the vial)....
somatostatin
AllieB2 says to (18:02):wake up *perfect*...
AllieB2 says to (18:02):stay perfect... all day
Dr. Pileggi says to (18:03):all right, time is up! Has been a great pleasure chatting with such an active crew
AllieB2 says to (18:04):Thank you so much, Dr. Pileggi!!
jon says (18:04):Thanks for chatting with us!
oopsy says to (18:04):thanks dr
tmana says to (18:04):Definitely... thanks :)
jon says (18:04):Thanks everybody for coming!
JIMBOB48 says to (18:04):THANKS DOC
sstrumello says to (18:04):thanks!!
Dr. Pileggi says to (18:04):talk to you soon. All the best
jon says (18:04):We will post a transcript tonight.
Dr. Pileggi says to (18:04):...ciao...
PhillyGuy says to (18:04):Thanks All
gina says to (18:04):thanks everyone
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