Stephen E. Gitelman, MD, is Chief of the Pediatric Endocrine Division at the University of California School of Medicine in San Francisco, California and he holds the Mary B. Olney, MD / KAK Chair in Pediatric Diabetes and Clinical Research. He is a clinical and translational researcher primarily involved in clinical trials with immuno-therapies to alter the natural course of type 1 diabetes—studies to predict risk for diabetes, and prevent it from occurring, and to preserve insulin producing beta cell function in those with recent onset disease. We sat down with Dr. Gitelman to discuss his JDRF-funded study of imatinib (brand name Gleevec):

JDRF: What motivates you in your research?

Dr. Gitelman: My maternal grandfather had type 1 diabetes (T1D), and was diagnosed not too long after the discovery of insulin. I grew up hearing stories about him and his trips on the train to the Joslin Center in Boston to pick up his supply of insulin. He was an early T1D pioneer and his experiences were talked about at our family dinner table. I also have two close relatives with T1D so I live every day saying that my three children don’t have T1D….yet. They and the families I partner with at UCSF who work hard every day managing T1D are my motivation to find a cure.

JDRF: How did the Gleevec study come about?

Dr. Gitelman: As JDRF knows, it is a long slow road from laboratory discovery to something that makes an impact in the clinic, and most things never make it that far. At UCSF, we look to find drugs that are previously FDA approved for other indications that may have an impact on T1D. Gleevec has been a blockbluster drug for treating some forms of cancer, and it has been found to be helpful for treating other conditions. For the diabetes world,  big news for Gleevec was from an animal study done in Jeff Bluestone’s laboratory back in 2009 showing that Gleevec can not only prevent diabetes in the NOD (Non Obese Diabetic) mouse, but it is one of only a handful of drugs that can actually reverse it. This powerful observation encouraged us to translate the effort into a phase 2 study for people with T1D. We feel that this is a very promising way to alter the natural course of T1D, and preserve beta cells.

JDRF: Why are you excited about the trial?

Dr. Gitelman: This drug works by a completely different mechanism than anything else that we have tried to date. Many of our past efforts have been very focused and targeted to a specific component of the immune system, primarily T cells, and yet we now appreciate the input from a variety of cell types during the autoimmune attack of beta cells. Gleevec affects a common signaling pathway in a variety of cells, and may help block the autoimmune and inflammatory response that occurs in T1D.  The further excitement for the trial (www.GleevecT1D.com) stems from the additional effects that this drug may have. It may help improve one’s sensitivity to insulin, so that a person needs less insulin to achieve blood sugar control. Gleevec may also have direct effects on the insulin producing beta cells themselves, helping prevent cell death and encouraging regeneration. A related drug has been FDA approved for a similar autoimmune condition, rheumatoid arthritis, and this adds to our hope that this may prove to be an effective therapy for T1D. Gleevec has been used in patients as young as age 3, so we know a lot about the safety profile of this drug. It has been very well tolerated to date in the patients who have entered the trial. And, unlike most of our other studies, the drug does not need to be given intravenously or by injection, but is a daily pill.

JDRF: Who can participate in the clinical trial?

Dr. Gitelman: This study is open to people with new onset T1D age 18-45 and pending FDA approval, we will lower the enrollment age to 12

JDRF: Do you anticipate that Gleevec will benefit people who have been living with T1D for a long time?

Dr. Gitelman: Absolutely. A person with long standing T1D has virtually no insulin producing cells or at least not enough to carry the day. The ultimate biological cure will be more beta cells (new cells made in a lab or regenerated cells of their own) AND some kind of treatment to prevent their bodies from attacking these new cells as they did their own cells years ago. All T1D research today will benefit the entire T1D community because we need to more fully understand the autoimmune destruction process. The Gleevec study and other intervention and prevention studies, like those being conducted by TrialNet (www.diabetestrialnet.org), are helping us get the answers we need to move forward towards a cure for everyone– those with new onset, those with long standing and our relatives who are at risk for developing T1D.

JDRF: Will participants be able to stop taking insulin? How will Gleevec impact their daily lives?

Dr. Gitelman: Great question and one I get all the time. When someone is diagnosed with T1D they have anywhere from 15-40% of their own insulin-producing beta cells remaining. That period of time is called the honeymoon. Having that undercurrent of beta cell function present, even if you still need to take supplemental insulin, can make a big difference in day to day management of diabetes. Managing diabetes without any beta cell function is like trying to ride a bike for the first time with no training wheels—the remaining beta cells are the training wheels, and can really help counter-balance risk for significant high and low blood sugars. Those cells can serve you well while they last, and it should be “easier” to maintain tighter blood sugar control, and ultimately help protect the body from long term complications. So, even though we don’t expect people to come off insulin, we do hope to extend the honeymoon for as long as possible.

JDRF: Where do we go from here and what’s the call to action?

Dr. Gitelman: Fasten your seatbelts because we are going to be moving fast and furious along the great highway towards more realistic and tangible cure therapies. The Gleevec study and others will definitely answer many of our questions but we need the help of the T1D community. We can’t do it alone.

If you are a family affected by T1D, please reach out to me and my team at UCSF to find out about the many opportunities to participate in research. If you don’t qualify for Gleevec, I’m sure there is another study coming soon or even a screening study for relatives.

Please contact Dr Gitelman and his research team at clinicalresearch@diabetes.ucsf.edu or toll free 1-844-T1D-UCSF or visit the UCSF Diabetes Center website for the latest listing of T1D clinical trials www.diabetes.ucsf.edu .