Comments on: The Sanford Project http://www.solvingdiabetes.org/2009/09/12/the-sanford-project/ A site dedicated to solving diabetes. Fri, 30 Jul 2010 02:09:31 +0000 http://wordpress.org/?v=2.9.2 hourly 1 By: Scott King http://www.solvingdiabetes.org/2009/09/12/the-sanford-project/comment-page-1/#comment-174 Scott King Tue, 15 Sep 2009 00:32:06 +0000 http://www.solvingdiabetes.org/?p=504#comment-174 JP, I agree with your sentiment, and of course that is one reason why I work on encapsulation. I would only add that regeneration can function with a reversal of the auto-immune sensitization which is narrower than the allo-immune sensitization that is the target of pharmaceutical immune suppression. Surely there are enough differences between allo and auto immunity that therapies that are limited to reversing auto-immunity are at least possible. At the very least specific desensitization to the known type-1-diabetes-specific antigens (e.g., GAD) might be effective. JP, I agree with your sentiment, and of course that is one reason why I work on encapsulation. I would only add that regeneration can function with a reversal of the auto-immune sensitization which is narrower than the allo-immune sensitization that is the target of pharmaceutical immune suppression. Surely there are enough differences between allo and auto immunity that therapies that are limited to reversing auto-immunity are at least possible. At the very least specific desensitization to the known type-1-diabetes-specific antigens (e.g., GAD) might be effective.

]]> By: JP Marat http://www.solvingdiabetes.org/2009/09/12/the-sanford-project/comment-page-1/#comment-171 JP Marat Mon, 14 Sep 2009 21:52:45 +0000 http://www.solvingdiabetes.org/?p=504#comment-171 For the islet regeneration/autoimmunity suppression project, it is vital that we get real about the massive toxicity of all existing immunosuppressive drugs. It would simply be foolish to trade type 1 diabetes for the side-effects of the present armamentarium for suppressing the immune system, which include nephrotoxicity, acute microvascular disease, electrolyte abnormalities, hypertension, hepatic dysfunction, hyperlipidemia, glucose intolerance, neurotoxicity, infection, a quadruple risk of cancer, thromboembolism, gout, leudopenia, anemia, skin ulcers, lymphopenia, psychopathology, leucopathy, atherosclerosis, and osteoporosis. On principle the severe complications of immunosuppressive treatment seem inevitable, since an intact immune system is a vital and natural aspect of the healthy human body. I have heard too many 'successful' heart transplant recipients receiving dialysis treatment say if they had only known how toxic the immunosuppressive drugs were going to be to their kidneys, they would never have opted for the heart transplant. If even heart transplant recipients calculate the cost/benefit balance of their procedure to be negative, then using immunosuppressive drugs to overcome type 1 diabetes -- a much less serious condition than the kind of severe cardiac insufficiency which requires a heart transplant -- seems a mere tour de force. Nothing could be more ridiculous than to rid the patient of hyperglycemia due to autoimmune-induced diabetes by using drugs which cause the patient to develop cyclosporine- and prednosine-induced diabetes, and then increasing the patient's drug-induced risk of renal failure to a greater degree than his diabetes-induced risk had caused. The search for better anti-rejection drugs with fewer complications has been going on now for about half a century, ever since the days when radiation, prednisone, and azathioprine were the only agents available. Aside from the calcineurin inhibitors which were developed in the late 1970s and introduced in the early 1980s, there has not been much progress with new medications making its way to clinical application. Brequinar, cyclosporine G, leflunomide, deoxyspergulan, and anti-adhesion molecule antibodies have all proved to be false leads. So to embark now on a complex, time-consuming, and expensive research program to cure type 1 diabetes on the mere hope that the future discovery of some relatively complication-free immunosuppressive will make it all rational seems to put the cart before the horse. For the islet regeneration/autoimmunity suppression project, it is vital that we get real about the massive toxicity of all existing immunosuppressive drugs. It would simply be foolish to trade type 1 diabetes for the side-effects of the present armamentarium for suppressing the immune system, which include nephrotoxicity, acute microvascular disease, electrolyte abnormalities, hypertension, hepatic dysfunction, hyperlipidemia, glucose intolerance, neurotoxicity, infection, a quadruple risk of cancer, thromboembolism, gout, leudopenia, anemia, skin ulcers, lymphopenia, psychopathology, leucopathy, atherosclerosis, and osteoporosis. On principle the severe complications of immunosuppressive treatment seem inevitable, since an intact immune system is a vital and natural aspect of the healthy human body. I have heard too many ’successful’ heart transplant recipients receiving dialysis treatment say if they had only known how toxic the immunosuppressive drugs were going to be to their kidneys, they would never have opted for the heart transplant. If even heart transplant recipients calculate the cost/benefit balance of their procedure to be negative, then using immunosuppressive drugs to overcome type 1 diabetes — a much less serious condition than the kind of severe cardiac insufficiency which requires a heart transplant — seems a mere tour de force. Nothing could be more ridiculous than to rid the patient of hyperglycemia due to autoimmune-induced diabetes by using drugs which cause the patient to develop cyclosporine- and prednosine-induced diabetes, and then increasing the patient’s drug-induced risk of renal failure to a greater degree than his diabetes-induced risk had caused.

The search for better anti-rejection drugs with fewer complications has been going on now for about half a century, ever since the days when radiation, prednisone, and azathioprine were the only agents available. Aside from the calcineurin inhibitors which were developed in the late 1970s and introduced in the early 1980s, there has not been much progress with new medications making its way to clinical application. Brequinar, cyclosporine G, leflunomide, deoxyspergulan, and anti-adhesion molecule antibodies have all proved to be false leads. So to embark now on a complex, time-consuming, and expensive research program to cure type 1 diabetes on the mere hope that the future discovery of some relatively complication-free immunosuppressive will make it all rational seems to put the cart before the horse.

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