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The Sanford Project
September 12th, 2009
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August, 2009 Science employment advertisement for six leadership positions
The biggest little-known effort to cure type 1 diabetes is called The Sanford Project. The project is a result of T. Denny Sanford’s extraordinary 2007 gift of $400 million to the University of South Dakota and the nonprofit Sioux Valley Medical System (renamed the Sanford Health System). Mr. Sanford made his money in the credit card business and is using his fortune to improve his native Sioux Falls with high quality health care and leading health care research.
One hundred million out of the $400 million gift was earmarked for a new initiative in children’s health. Aside from his wish to help children, Mr. Sanford’s other express desire is to live to see the resulting benefits. Battelle Memorial Institute was retained to evaluate the research opportunities and then develop a list of the four most promising children’s health initiatives. Of the four opportunities presented, Sanford Health selected islet regeneration for type 1 diabetes as The Sanford Project. (Mr. Sanford does not have a close personal interest in type 1 diabetes, rare for type 1 diabetes donations.) Thus the Sanford Project in Sioux Falls is a new and well-funded attempt to cure type 1 diabetes through regeneration of islets of Langerhans.
Having no previous special emphasis on diabetes, the Sanford Health System began with few clinical or research assets. Since the announcement of their decision to focus on type 1 diabetes in July 2008, they have hired four key researchers, begun development of a research center for The Sanford Project in Sioux Falls, and laid the groundwork for their first clinical trial. The most important step was finding a Director for the Sanford Project. The Broin family of Sioux Falls donated $10 million to endow a chair for the Director making it possible to attract the best diabetes research leadership.
In July 2009 the Sanford Project announced that Dr. Paul Burn had been appointed to the Todd & Linda Broin Chair, Director of the Sanford Project. I have known Paul a few years, since his arrival at JDRF where he was Senior Vice President of Research. For me he was a ray of hope at JDRF, an organization whose accomplishments have fallen short of their goals and promise. Paul had worked in the pharmaceutical industry and knows how to get products to the market. His job was to transform JDRF’s research portfolio into clinical advances; considerable progress was made under his leadership. JDRF’s funding began to decline a year ago and there was no money for new initiatives. The Sanford Project is well funded. Paul Burn decided to take their offer to lead The Sanford Project.
Although Sioux Falls is a major health center it is not yet known for its research. It is a livable city, with the lowest unemployment in the country, but it is far from the glamorous coastal research centers and might be regarded as a difficult city to attract researchers. Sanford’s progress in recruiting during its first year belies this notion. At The Sanford Project web site you can read about their first three scientists, Da-Qing Yang, Alexei Savinov, and Alexander Rabinovitch.
The goal of all type 1 diabetes therapy is to normalize metabolism so that vascular decay is eliminated. At Cerco Medical we are working on a form of islet replacement therapy that works by protecting the islets from the immune response in a thin sheet device with a protective membrane, the Islet Sheet.
The goal of islet regeneration is not to replace the islets but rather to make the diabetic’s own tissues regenerate functioning islets. This poses two major challenges. The first is to make non-islet tissues differentiate into islets and grow to full functionality. The second is to suppress the ever-present islet autoimmunity. All type 1 diabetics have T cells primed to destroy islet cells when they are diagnosed with the disease and for the rest of their lives. Both islet differentiation and islet autoimmune suppression are very difficult to achieve because they rarely happen spontaneously. For islet regeneration to work, both these difficult biological engineering tasks must be done simultaneously. It seems likely to me that when islet regeneration is eventually successful it will be a combination of at least two pharmaceuticals, one an innovative immune suppressant, one an islet differentiator.
Dr. Burn recently placed this advertisement, so we are in the position to discern his strategy for staffing The Sanford Project. He is proposing that their basic and clinical research be organized into six areas. Clearly he understands that regeneration and autoimmunity are the key issues. But notice too that leads will function on three levels from cells to animal models to clinical (called “translational”). Most academic efforts focus on cells and do little for the higher levels of investigation. Given Paul’s industry background, combined with his emphasis on translational research, The Sanford Project has the promise of achieving clinical results in islet regeneration as rapidly as they can be achieved.
I was in Sioux Falls last week to talk to Paul about his work at Sanford and to tell him about our progress at Cerco Medical. He believes that the great opportunity for the Sanford Project is in clinical work. He has access to a big health system rarely used for clinical studies: last year the Sanford Health system had over a million patient interactions. He says that almost the entire clinical infrastructure is in place. For instance, he believes that the ten years of research that Alex Rabinovitch did at Edmonton on islet regeneration will translate into a clinical study at Sanford soon.
How long could it take for a clinical breakthrough in islet regeneration? Dr. Lakey, our collaborator on the Islet Sheet, has said that we should have clinical results for our Islet Sheet islet replacement approach within two to four years. I think islet regeneration will take longer. It will start with therapies for newly diagnosed type 1 diabetics. These patients are the most promising because they have natural ongoing islet differentiation. Pharmaceutical therapy that suppresses the autoimmune response has been proven already to extend the ‘honeymoon’ that diabetics experience, probably by allowing natural islet regeneration to proceed longer. So I can imagine therapies that extend the honeymoon of newly diagnosed diabetics becoming avaiable relatively quickly, perhaps in five to ten years. But fully developed diabetics (like me) still have autoimmune disease and have completely lost natural islet regeneration. Based on my thirty years’ of diabetes research I think fully effective islet regeneration for all people with type 1 diabetes will probably take decades.
From all I have seen The Sanford Project under Paul Burn’s leadership is the most promising effort in islet regeneration. Given its leadership and resources, and their desire to be the clinical innovators, it looks likely that the reality of islet regeneration will be known and shown first in Sioux Falls.
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.
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.