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Under the Microscope with Jay Skyler, M.D.

While researchers know that type 1 diabetes results from autoimmune destruction of the insulin-producing beta cells in the pancreas, they do not know how to stop this attack – at least not yet. That is one of the primary goals at the Diabetes Research Institute, where scientists are intensely focused on tackling the immune challenges that are critical for discovering a biological cure, as evidenced by the new clinical trials on the horizon.

Thus far, preventing and reversing islet cell autoimmunity has eluded scientists, as Dr. Jay Skyler knows all too well. With a career that spans more than 50 years, Dr. Skyler, who serves as Deputy Director for Clinical Research and Academic Programs, has led countless clinical studies, the majority of which have focused on regulating the immune system to halt beta-cell destruction.

Now, armed with decades of clinical experience and important data emerging findings from a variety of immunological studies, Dr. Skyler, together with his multidisciplinary team of colleagues at the DRI, is developing new immunotherapy-based approaches that may ultimately achieve this goal and benefit the millions living with T1D.

You have been involved with countless diabetes research initiatives to prevent and reverse type 1 diabetes. What has been learned so far? Why is T1D such a challenging disease to conquer?

是的,这是一种复杂而具有挑战性的疾病,因为T1D的演变不涉及一种,而是几种免疫途径,这使设计和测试可能是“理想的治疗策略”的复杂化。

The majority of the past clinical trials involved the administration of single agents and have primarily targeted the immune system. However, there is growing evidence that type 1 diabetes is a multi-factorial disease – that other things like inflammation and beta cell dysfunctions may also be important in the development and propagation of the disease process, and therefore we should look carefully at these in crafting an intervention that might arrest the disease process.

What research approaches are underway at the DRI to address these immune system challenges?

We’ve seen that scientists have had success in applying a combinatorial approach to patients with HIV and cancer, which are also diseases involving multiple pathways. This concept needs to be applied more extensively to T1D. Data emerging from our own clinical islet transplant trials, together with studies conducted by other research groups, have already demonstrated better outcomes in type 1 diabetes onset and progression using some combination of agents that target key immune system pathways. This is, in fact, is what has led us to the next planned study design for one the DRI’s newest clinical trials now in final planning stages: DIPIT.

Can you tell us more about the DIPIT trial and what is the DRI is looking to achieve?

糖尿病胰岛保存免疫治疗(DIPIT)试验使用的药物至少在T1D中是有益的,至少是瞬时对T1D有益的,并将其结合在时间和剂量方面,以测试一种免疫系统调节的新组合方法。结合使用,这些FDA批准的药物(有些是非常低剂量的药物,有些在短时间内)可能被证明具有独特的能力,能够靶向我们需要的几种特定免疫途径,以在最近的发作T1D患者中保留胰岛素分泌。许多医疗中心已经表示有兴趣参加这项多中心试验,这将是对此类试验进行的第一次此类试验。

是什么让糖尿病患者成为如此激动人心的时刻?

While I don’t think there will be one single “magic bullet,” I think that there will be a variety of different approaches that we might use at different times in people with different characteristics. I think the field is moving in that direction, and I think some time in the future we will be able to prevent type 1 diabetes, perhaps be able to stabilize type 1 diabetes and keep beta-cell function going for a protracted period of time, and we will be able to replace beta-cell function in people who have already lost it. I want to see this disease cured in my lifetime, and I am highly enthusiastic in where the future is going. With dedicated people working on it and the resources needed, we will beat it.

Why did you choose to focus your career in diabetes?

我在1967年糖尿病,开始做研究in medical school and I remember distinctly I was working in a small room and had been assigned to stage diabetes eye disease in patients based on pictures of their eyes. I asked my mentors if I could follow them as they did their rounds, and what I saw and experienced then on the floors of the hospital impacted me so profoundly that it charted the course of the rest of my professional career. Patients very similar to me in age were already going blind from diabetic retinopathy, and there wasn’t a good therapeutic intervention anyone could offer them that truly worked; I knew then this was the area I wanted to contribute to professionally.

We’ve come a long way and learned a great deal since then about the disease and its unfortunate complications. Robust investigations continue to be directed at interrupting the type 1 diabetes disease process in an attempt to prevent and/or reverse its development. Significant advances have been made in not only diabetes care, but also in patient self-management, in insulin types, in glucose monitoring and many other related areas but we still don’t have a cure in hand to offer patients and that’s frustrating.

(Drifocus 2017年秋季)

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