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| Podcast title | GTCbio's Research Bulletin: Biotech and Pharmaceutical Industry Update
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| http://gtcbio.podomatic.com | ||
| Description | Interviews of top scientists on the latest research and new developments in the biotech and pharmaceutical industries. | |
| Updated | Sat, 14 Jan 2012 03:44:18 GMT | |
| Category | Science & Medicine |
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1. Transplantation and Beyond http://gtcbio.podomatic.com download (, 0.00Mb) Description: With Aaron I. Vinik, M.D., Ph.D. , Professor of Internal Medicine; Director, Strelitz Diabetes Institute Pancreas transplantation has provided a cure for many insulin dependent diabetic patients. By the end of 2005 there were about 25,000 done worldwide, 18,000 of these in the . The 3 year survival has now reached 95% for pancreas alone, pancreas and kidney and staged kidney pancreas procedures. That this is really designed to address people with advanced disease who need a kidney is borne out by the high mortality approaching 40% in those on the waiting list. In addition the need for of immunosuppressive therapy on a lifelong basis are not without hazards but graft function for 3 or more years occurs in 75-80% of cases and for some unknown reason is better with a staged procedure. This is highly efficient but major surgery and clearly desirable in patients needing a kidney! Islet transplantation prior to the year 2000 was feasible but the islet survival was dismal, the need for immunosupression great, and the freedom from taking insulin rare. With the introduction of the Edmonton protocol which utilize 2-4 pancreases, avoids the use of steroids and uses a relatively benign immunosuppressive approach the possibility that a cure could be accomplished successfully essentially eliminating surgical risks associated with whole pancreas transplantation loomed loud and clear. The original Shapiro data suggested insulin independence in only 10-20 % of patients despite improved C peptide after 48 months. In a multicenter trial using this protocol there are some centers e.g. Miami that have achieved a greater rate of insulin independence while others have failed dismally. The argument is that even a small amount of insulin may reduce the burden of diabetic complications. Ther are however major needs to improve immunosupression and techniques such as nanoencapsulation and the use of a variety of non toxic immunosuppressant agents is actively being pursued. However the availability of pancreases is seriously limited + 8000/year and it take 2-4 for a successful transplant limiting the procedure to about 1500/y clearly an embarrassingly low number considering the deserving patients who are out there in need of help. Alternative methods are clearly needed to provide functioning islets. Until recently it was considered heretical to even dream of expanding islet mass. It is now evident that there are several ways in which islet mass can be expanded by causing hypertrophy, hyperplasia, and replication of preexisting beta cells or, by inducing neogenesis of new w islets derived form protodifferentiated stem cells resident in the human pancreas for as long as patients have been examined. Balancing these forces are those that cause apoptosis or necrosis of pancreatic beta cells such as autoimmune destruction of islet in type 1 diabetes and programmed cell death probably mediated by hIAPP in type 2 diabetes so that the onset of the disease there is already a 50% loss of islets and there is a progressive decline at the rate of abut n6-10%/y. Recent evidence suggest that a number of growth factors can initiate growth, proliferation, differentiation of these precursor cells in vivo into functioning islets capable of secreting insulin in a regulated manner and of curing diabetes in animals and mitigating its severity in humans. The growth factors include INGAP, gastrin and EGF and each has its own merits and demerits. The need for prevention of destruction by autoimmunity is still present and retardation of the apoptotic process may be achievable with GLP-1 analogues, the TZDs or DPP1V inhibitors. We are at the dawn of an era of regeneration of pancreatic islets from pancreatic acinar tissue. The process requires protodifferentiated stem cells. The first agent shown to promote islet neogenesis was INGAP. It has now bee shown to not only promote islet regeneration but protect the beta cells from destruction. In addition the concern with unbridled cell proliferation may not be as great a concern with this peptide since it had been established that there is a negative feedback loop as a restraint mechanism limiting unbridled growth and proliferation. The mechanisms of this process are being elucidated. There are a number of critical issues that need to be addressed to translate theses observations into clinical care. But conservatively, from a not uninvolved perspective the future promises great advances in the de novo production of islet tissue in diabetic patients as a “cure” for some forms using INGAP alone or in combination with immunosupression or other trophic and antiapototic agents. Dr. Vinik will be covering this topic in greater detail at GTCbio's 3rd Metabolic Diseases World Summit. November 1,2 2007 in San Diego. |
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