Commentary
In a recent Juvenile Diabetes Cure Alliance survey, 57% of patients with Type 1 diabetes say they expect a cure by 2025. Why only 57%? Why should we have to wait until 2025? As a Type 1 diabetes researcher and clinician, it is my firm belief that we could have achieved insulin independence for people with Type 1 more than a decade ago. The problem is that to get there requires a new way of thinking.
Our scientific team at Perle Bioscience has data to support the idea that insulin independence among people with Type 1 will require combining two totally different types of treatments that often aren’t paired together. This is not a radical idea; combination therapy has become the predominant pathway to life-saving treatments for cancer and HIV.
For decades, researchers have known that Type 1 diabetes is an autoimmune disease—a disease in which one’s own immune system accidentally sees insulin-producing cells as foreign invaders to attack. The attack often occurs after an infection, when the body is primed to attack something and, like a drunk in a barfight, somehow picks a fight with the wrong cells.
What we have learned from 3 decades of studies is that immune-blocking therapy to protect the insulin-producing cells of the pancreas simply doesn’t work in humans the way it does in mice. Unlike more than 300 studies in mice that show T1 can be reversed by simply using an agent to block the immune attack on the pancreas, the same does not hold true in humans. Mice can regenerate insulin-producing cells much better than man, so humans need help.
As work has progressed on ways to block attacks on insulin-producing cells, other teams of researchers have developed methods of generating new insulin-producing cells in humans. Again, this isn’t new; surgeons have reported for almost a century that clamping off the pancreas generates new insulin-producing cells. More recently many research teams have shown that insulin-producing cells are generated as result of a gene protein whose sole job is to regenerate them; this protein is appropriately named Reg. Several recent studies in human and mouse pancreata have shown that Reg generates new insulin-producing cells directly from duct cells of the pancreas, which make up 98% of the pancreas.
(Fun fact – Doing the math, that means that only 2% of the cells of the pancreas actually generate insulin and other hormones necessary to maintain glucose levels within a normal range.)
About 15 years ago, I was fortunate enough to be a researcher in a fascinating study among patients who had Type 1 diabetes for an average of 20 years and had no detectable C-peptide in their bloodstream; C-peptide is the marker of internal insulin production. The study gave these patients daily Reg therapy, and by day 54 there was a 27% rise in C-peptide.
Statistically, boosting C-peptide production by just under a third is remarkable, but it’s not the end of the story. Mice can keep the new insulin-producing cells and can go back to carefreely making insulin again, but the human body will attack the new insulin cells if left to its own devices. Humans need some kind of shield to protect these cells or we eventually start back at square one.
The teams of scientists who have worked on protecting the pancreas from autoimmune attack are immunologists. The teams that have worked on new therapies for regeneration of insulin-producing cells are endocrinologists and surgeons. Unfortunately, these different types of scientists do not cross paths as often as they should. The only way to get to a practical cure is to get these two groups to play nicely together and get to know each other’s work.
Recently, our team held a worldwide summit that brought together leading regeneration researchers and immunologists. At that summit, we came to a singular conclusion: insulin independence for people with T1 diabetes requires both immune tolerance and regeneration. We agreed that combination therapy is the best potential road for insulin independence now, not just in 2024. Findings of the summit can be found at www.InsulinIndependence.com and in the peer-reviewed journal Diabetes/Metabolism Research and Reviews at http://www.ncbi.nlm.nih.gov/pubmed/23853103.
Finding a practical T1 cure is not a matter of finding a new scientific discovery; it’s about making something greater out of the parts of what we already know.
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