JDRF nPOD Conference Highlights Innovation in Prevention and Cure Research
.jpg)
By Amy Liang
Type 1 diabetes has been prevented and cured in more than 500 ways in mice, but never in humans. nPOD researchers are trying to change that, one donated organ at a time.
The majority of type 1 diabetes research today uses mice or other animal models of the disease. While this type of research has taught us plenty about type 1 diabetes, many experts now believe that in order to better understand diabetes in humans and develop a cure, more research needs to be done using human samples, including pancreatic tissues. nPOD – Network for Pancreatic Organ donors with Diabetes – was founded in 2007 in response to that need, with the goal of supporting research using tissue samples from human organ donors.
This year, we had the opportunity to attend the JDRF nPOD conference, which brings together researchers in the type 1 diabetes research community from around the world to present their latest findings and partner across research teams. While at the conference, we interviewed the following (remarkable!) nPOD leaders to learn more about its origins, its current research, and its potential for impact:
- Dr. Mark Atkinson, nPOD Executive Director
- Dr. Desmond Schatz, the incoming American Diabetes Association (ADA) President
Read our interview below to learn their thoughts on new discoveries, challenges, and the future of type 1 diabetes research.
Interested in supporting nPOD? You can join the nPOD community, whether as an organ donor, nPOD partner, or an investigator.
Q: Can you please describe why nPOD started?
Dr. Atkinson: I became personally concerned about depending too much on mice for diabetes research some 10 years ago. People thought that a type 1 diabetes cure was on the horizon because there were literally hundreds of ways to prevent or cure diabetes in mice. Yet today, the number of ways to reverse the disease in humans still remains zero. Using mouse models has provided benefit but in many other ways, I believe they also led us astray to some degree. Mouse models have proven of value in many aspects of diabetes research, perhaps the most favorable being in the field of stem cell research, but in terms of therapeutics, their impact has been minimal. So many treatment methods that work on mice do not work on humans, likely due to anatomical differences between the islet and beta cells of the two species as well as variances in their immune systems.
Three or four decades ago, autopsies were more common for providing researchers with human tissue samples, but due to the rise of animal models, autopsies for human tissue research have decreased to the point of extreme rarity. We need to go “back to the future.” nPOD is a real movement to try to understand what is happening in humans, and that is really unique.
Q: What are some research questions that nPOD resources can help answer that simply could not be addressed without actual tissue or organ samples?
Dr. Schatz: Using actual tissue or organ samples allows us to ask the question, “What is happening in the human pancreas?” This is a vital question because we really don’t fully understand type 1 diabetes. We really don’t know the mechanism and causes behind type 1 diabetes. We know it is the end result of self-destruction of beta cells, predominantly by CD8 T cells. Why this occurs, we don’t know. The hope for nPOD is to allow us to study the pancreas and other tissues to get insight into the mechanisms of human type 1 diabetes. We study various aspects including the role of the immune system, genes, and the environment (e.g., infectious agents) to better understand the process leading to the disease. We hope to re-write the textbooks on type 1 diabetes.
Q: What successes has nPOD seen, and what challenges has it faced?
Dr. Atkinson: Funding has gone well – we have gotten a lot of support from the Helmsley Charitable Trust, JDRF, NIH, and ADA. What could go better is to find a way to message the importance of nPOD’s mission and avoid controversies associated with death. While at this meeting, I was to meet some individuals about research in type 1 diabetes but they elected not to meet, noting they didn’t want to talk about “slicing and dicing a child.” Any type of talk about death is unpopular. While clearly a difficult subject, I only wish people understood the dramatic – and I do mean dramatic –insights we are gaining about type 1 diabetes through nPOD. Beyond this, we treat each donor and their family with the utmost respect, along with deep gratitude. We are always sensitive. [Editor’s note: Wow, this is fascinating. How can we change the perception of organ donor research? Let us know if you have ideas…]
Another barrier we face is the misconception that people with diabetes cannot be organ donors. Every year, 2.5 million U.S people die, but there are only 8,000 solid organ donors for transplant and 5,000 organ donors for research. Because of the need for kidney transplants in individuals with type 1, beyond research, I think there is a great need to help improve on the low rate of organ donation. This must be a community effort for both type 1 and type 2 diabetes. If everyone with type 1 or their family member would agree in principle to be an organ donor, it would greatly increase our odds of obtaining the pancreatic tissue samples we need.
Q: What projects are you most excited about?
Dr. Atkinson: I am excited about everything, but particularly interested in the “small pancreas project,” which started as a result of reports in the mid-1980s. Researchers noted from studies of autopsy cases that a person with type 1 diabetes had a smaller pancreas than someone without diabetes. At the time, it was unclear if this stemmed from the organ sitting in a cooler or whether the tissue had degraded. Now we believe that humans are born with a normal sized pancreas, but at the onset of diabetes, the pancreas is 25-35% smaller than that of people matched in age and size. The diabetic pancreas then becomes 40-50% smaller than a normal pancreas within a year of diagnosis, at which point it stabilizes. Since beta cells comprise only 1-2% of the pancreas, other parts of the organ must play an important role in diabetes, and I’m excited to discover what that is. This, because it may be important in determining an answer to the question of what causes type 1 diabetes.
Additionally, I am interested in determining how many beta cells an individual has, and if beta cell-count is a risk factor for type 1 and type 2 diabetes.
Finally, I am fascinated by the role of beta cells in type 1 diabetes. 90% of cure therapies are directed at preventing CD8 T cells [immune cells] from killing beta cells, but what is the role of the beta cells themselves? In particular, I am interested in beta cell stress: how does it impact the occurrence of diabetes? How does it relate to the development of type 2 diabetes?
Q: What are the future challenges?
Dr. Atkinson: It is currently the best of times and the worst of times. It is the best of times in regards to the ideas, information and technologies. Unfortunately, funding is difficult to obtain. NIH grants have a 90% failure rate. Unable to obtain sufficient funds, many intelligent PhD students turn to other careers and MD’s practice medicine without performing research. I fear the aging investigators and the loss of multiple generations of bright young researchers and physicians. The academic physician, especially those that specialize in pediatric diabetes, is a declining career path as a result of the high failure rate.
Another challenge we face is that with the rise of disruptive technology (such as the artificial pancreas, stem cell-derived functional cures, etc.), there will be better and better alternatives that less people will be willing to partake in clinical trials.
Q: What are your long-term goals for nPOD?
Dr. Schatz: I would love to see greater awareness of nPOD. As a clinician, I want to give patients hope and that is only possible by learning more. nPOD’s success rests on building an understanding of how diabetes develops, and how we can advance therapies to prevent and cure type 1 diabetes biologically. The ultimate goal is to make all our patients’ lives easier.
