Dr. Aaron Kowalski joined the JDRF (Juvenile Diabetes Research Foundation) a few years ago as strategic director of research, and heads the organization's exciting Artificial Pancreas Project -- a multi-million dollar initiative for accelerating development of a "closed-loop automated insulin-delivery system." In this role, he now works with more than 20 companies creating new diabetes technologies for improving blood sugar control in people with diabetes. Besides being an incredibly smart and personable guy, he's also got the full-on passion for this stuff that can only come from living with diabetes yourself. Aaron and his brother Stephen were both diagnosed with Type 1 diabetes as kids, and have lived with it for over 22 and 29 years respectively. He was kind enough to share some year-end insights with me and the readers of DiabetesMine.com.
The mission of the JDRF hasn't changed at all: to cure diabetes and its complications through the support of research. The JDRF Artificial Pancreas Project arose because of the potential for an artificial pancreas to reduce the risk of complications and increase the likelihood of success of cures focused on the immune response that causes diabetes and the transplantation and regeneration of insulin-producing islet cells.
As you know, there is extensive research showing that good glucose control prevents diabetes complications; but most people with diabetes have a very hard time achieving it. In fact, a recent study showed that even intensively managed people -- doing nine fingerstick tests daily -- spent less than 30% of the day in a target glucose range (70-180mg/dL). Similarly, the NIH-funded DirecNet found that children with an average A1c of 6.8% -- which is obviously good -- spend nearly 9 hours per day above 180mg/dL! Take those results, and then remember that the average A1c in the United States today is over 8%. This says to me that if a key aim is to prevent complications, we need better tools to help people with diabetes achieve tight glucose control. Plus, one of the major reasons that people with diabetes experience hyperglycemia (high blood sugar) is hypoglycemia (low blood sugar). If we didn't have to worry about getting low, we could inject more and more insulin until blood sugar levels were just right. As you know, that's not currently the case; just a little too much insulin at the wrong time can cause a serious low. These new technologies have the potential to help with both high and low blood sugar, which would be a first.
An artificial pancreas not only holds the potential to help with glucose control. As you know,
one of the hardest parts of living with diabetes is the constant mental burden
24/7/365. How much did I eat? Should I have a bedtime snack? Why is my blood
sugar high/low now? How many carbs? Etc... This device can alleviate some or most
of the mental burden of diabetes, which I think would be huge from a quality of
Finally, we believe that an artificial pancreas will help us get to our ultimate goal sooner: a biological cure that will enable us to walk completely away from diabetes. We know high blood sugar is bad for cells —- particularly cells that are sensitive or at risk, such as transplanted or regenerated beta cells in a person with diabetes. The tight metabolic control an artificial pancreas would provide will enable cures aimed at maintaining beta cell mass, or restoring normal blood sugar through transplants or regeneration, to be more effective. I believe that we'll see successful combinations of mechanical artificial pancreas technologies and biological approaches in clinical trials in the near future.
What are your personal goals for advancing the AP project?
I joined the JDRF in the fall of 2004 working in the area of diabetic complications. My background is in molecular biology and biochemistry and my motivation was to make an impact in an area that has affected my family considerably. Both my brother and I have lived with Type 1 diabetes since we were children. My brother Steve (who is 2 ½ years younger than me) was diagnosed when he was 3 and I was diagnosed when I was 13. Hypoglycemia had a very significant and regular impact on us over the years, unfortunately.
Steve is very hypo-unaware and as a result has spent a considerable amount of time visiting the emergency rooms of New Jersey hospitals where we lived. The idea that a mechanical system could help him prevent many of these events was a dream for our family. We are already both benefiting from continuous glucose monitoring technologies. Both of our experiences with the devices have been fantastic. That said, my main goal is to bring automation to the system -— to close the loop. As fantastic as the CGM has been, there are still limitations -— diabetes is still hard -— and automation, I believe, is an achievable goal. We have demonstrated this in studies at a number of the JDRF Artificial Pancreas Project research sites. The goal is to translate this research into a system that is available for all people with diabetes to benefit from.
The main thing the JDRF is doing is to continually focus upon driving the pace of science leading to a cure by moving research from basic academic discovery into the development of treatments and potential cures. And we're increasingly focusing on the gaps that currently exist in the pipeline to take those ideas and basic research findings and translate them into drugs, treatments, and products that are available to people with Type 1 diabetes.
There are a few excellent signs of progress in this regard. For example, we've dramatically increased the number of human clinical trials in all of the areas of research that we're funding. At the beginning of the decade, the science we funded included perhaps five human clinical trials. Today, as a result of an intensive focus on developing what we call cure therapeutics over the past half decade, we are now funding more than 30 human clinical trials.
Another clear sign of progress is our ability to fill gaps in the clinical development pipeline by forming partnerships with industry, usually small companies, to help accelerate the treatments that are brought to market for people with all stages of diabetes. We've partnered with more than 20 small companies involved in biotech, genetics, immunology, transplantation, and regeneration who have products and treatments in the early stages —- products that need proof-of-concept funding that is unavailable from large pharma companies or venture capital firms. By taking on this role, our strategy has been to "de-risk" the early stage clinical trial investigation of these cure therapeutics, in order to carry them through the pipeline to the stage where a large company would be willing to pick them up, take them through large scale trials needed for FDA approval, and commercialize them. We've already had two success stories: just this October, two small biotech companies for whom we helped fund early stage clinical trails for drugs that prevent the progression of diabetes in newly diagnosed patients signed partnerships with major diabetes companies to carry those products through the final stages of testing and make them widely available in the marketplace.
What are some of the hottest companies involved, and why?
We're currently involved in feasibility studies with a number of outstanding diabetes device companies. JDRF-funded investigators are using Abbott, DexCom, Insulet, Medtronic, and Smiths devices. Our goal is to see a thriving market, in which multiple companies are developing outstanding technologies that help people with diabetes achieve better outcomes. Furthermore, we want an environment where research into better and better (smaller, more convenient, more effective, etc...) systems is rewarded so that all people with diabetes have a chance to benefit.
What were some of the biggest milestones in 2007 -- for the JDRF, and also for the field of diabetes treatment on the whole?
Clearly, the progress I talked about above was huge for JDRF and diabetes in general in 2007: first, the number of treatments and potential cures studied in human clinical trials, including several in Phase III trials -- the last stage before FDA approval. And secondly, this provided validation of our strategy of funding early gaps in the diabetes product development pipeline, by having two compounds picked up by major pharma companies.
We've also made tremendous progress in several areas of diabetes complications over the past year, particularly retinopathy. And I'd be remiss if I didn't point to my own area of responsibility with the JDRF Artificial Pancreas:
- We'vecompleted enrollment of more than 400 patients in the JDRF CGM trial, whichlooks to provide independent statistics on the effectiveness of CGMs, with anaim of speeding reimbursement and clinician adoption of thetechnologies.
- We'vesuccessfully closed the loop -— teaming CGM with an insulin pump system -- inchildren for the first time in an early feasibility trial at Yale University.
- We'vefunded seven research sites around the world that are focused on perfectingclosed-loop systems, including creating algorithms to safely and effectivelydirect insulin delivery based on continuous glucose monitoring readings, taking into account the whole range of variables that people with diabetescurrently have to calculate on their own, from current blood sugar, to thedirection it's trending, to what and how recently you've eaten, to the impact ofexercise, to an individual's sensitivity to insulin.
- We've also partnered with the FDA to begin to clarify the regulatory pathway to anartificial pancreas, which the FDA has made a "critical path" goal.
What can we expect from you and the JDRF in 2008?
In general, our focus is on continuing to speed the pace of research leading to a cure across our five cure therapeutic areas. In autoimmunity, we are looking to better understand what causes the autoimmune attack that causes diabetes, and prevent it in people who are at risk for the disease, and reverse for those who already have diabetes. In regeneration, we are looking to develop compounds that spur the body to regenerate insulin-producing cells without the need for their surgical replacement. In replacement, we are looking for ways to improve the effectiveness of current transplant procedures, explore alternative replacement opportunities, and develop additional sources of insulin-producing cells. In complications, we are researching ways to reverse or prevent complications ranging from eye disease to kidney disease to peripheral nerve damage. We are looking at funding as much as $170 million in science in our current fiscal year.
Specifically in my area, metabolic control, once results
from JDRF's CGM trial are available, we plan to launch a patient advocacy effort
to advocate for formal insurance coverage and reimbursement of continuous
glucose monitors. We will also accelerate our work to develop an artificial
pancreas, funding research to test and refine algorithms to make them more
effective for real world situations such as meals, exercise, and stress;
integrate them with next-generation glucose monitoring and insulin delivery
technologies, and test the safety and effectiveness of these systems in clinical
Wow, thank you, Aaron for providing us with hope. So much for the sinking feeling that progress toward a cure is sluggish at best. Go, JDRF!