Silencing immune attacks in type 1 diabetes

by Tripp Underwood on June 10, 2013

Could diabetes be treated without insulin shots? (Tess Watson/Flickr)

Could diabetes be treated without insulin shots? (Tess Watson/Flickr)

For decades, patients have managed their type 1 diabetes by injecting themselves with insulin to regulate the glucose in their blood. While this form of medical management addresses the immediate danger of low insulin levels, long-term complications associated with diabetes, like heart and kidney diseases, still threaten more than 215,000 children currently living with the disease in the United States.

“Insulin injections can manage hyperglycemia by reducing the patient’s glucose levels, but it is not the cure,” says Paolo Fiorina, MD, PhD, of the Nephrology Division at Boston Children’s Hospital.

Fiorina is currently involved in new research targeting a molecular pathway that triggers diabetes in the first place—potentially providing a permanent cure. It could potentially change the face of diabetes treatment in children.

For decades, researchers have experimented with cell transplantation as a possible way to cure diabetes. The first breakthrough came in the early 1970s, when a pair of scientists successfully transplanted insulin-secreting pancreatic cells from one rat to another, reversing the recipient’s diabetes.

By the early 1990s, the Diabetes Research Institute in Miami had performed six successful pancreatic islet transplants in humans—evidence that the procedure can lead to long-term reversal of diabetes. The procedure takes islet cells from the pancreas of a deceased donor and injects them into the portal vein of the recipient’s liver (an organ that’s better able to withstand transplant than the pancreas). Once enough islet cells are in the liver, they begin to produce and secrete insulin as they normally would inside the pancreas. No more insulin injections.

Fiorina

Fiorina

Despite the initial successes, though, further islet transplants have been plagued with mixed results. Even when the transplants are successful, patients require immunosuppressant medications to prevent their immune system from attacking the transplanted cells—medications that come with their own, potentially serious, side effects.

In fact, in many cases, cell transplant seems to trade one unhealthy immune response for another. “Both diabetes itself, and its potential cure by way of cell transplantation, are plagued by the same problem—the immune system attacks the islet cells,” explains Fiorina. “In order to truly cure diabetes, we needed to pinpoint exactly why this happens. And then prevent it.”

Fiorina and his team studied hundreds of pathways in animals with diabetes. They eventually isolated one, known as ATP/P2X7R, which triggers the T-cell attacks on the pancreas, rendering it unable to produce insulin.

“By identifying the ATP/P2X7R pathway as the early mechanism in the body that fires up an alloimmune response, we found the root cause of diabetes,” says Fiorina. “With the cause identified, we can now focus on treatment options. Everything from drug therapies to transplants that require less immunosuppression is being explored.”

The findings were published online-before-print by the journal Diabetes in January. And while Fiorina and his team are still a few years away from testing these therapies in children, the implications for their success would be substantial.

“I believe it won’t be long before we can cure diabetes with a number of different therapies depending on the needs of the patient,” he says. “Then, if the right screening techniques for diabetes could be developed, it would be entirely possible in many cases that we could prevent the disease from ever developing in children. The future of diabetes treatment is very exciting.”

12 comments

  • Heather Etchevers

    Advancing the understanding of root causes is always very exciting. However, we may still be far from a cure. A very similar reason for the depigmenting condition, vitiligo, has been identified, but treatment options remain the same. Rheumatoid arthritis also comes to mind. Selectively taming the immune system is not a walk in the park, but I congratulate the Fiorina group for taking a step in the right direction.

  • http://khurtwilliams.com/ Khürt L. Williams

    “Fiorina is currently involved in new research targeting a molecular pathway that triggers diabetes in the first place—potentially providing a permanent cure. It could potentially change the face of diabetes treatment in children.”

    http://jdrf.org/about-jdrf/fact-sheets/type-1-diabetes-facts/

    Approximately 85 percent of people living with T1D are adults. What about us?

    • Kate Patterson

      My thoughts exactly! It’s amazing to me how even those in the field forget that it’s type 1 is not just a kids’ disease.

    • nansona

      We referred this question to Dr. Fiorina; here’s his reply:

      “85% of patients with T1D will benefit, because any therapeutic approach used to replace beta cells in this population (either stem cell based or islet tx based) will be blunted by the recurrence of autoimmunity.

      Thus we will need to target autoimmunity in patients with long standing T1D. No matter what stage of T1D you are, immunotherapy could potentially benefit you.”

      –Nancy Fliesler, Editor

      • betsy

        Who are the 15%? Those who would be excluded due to other factors? Still, the nature of the blog post should be edited to eliminate wording around children. Yes, children exude an emotional response, but if your audience is patients, their families, and the wider scientific community, then please let go of that juvenile onset language- it only reinforces stereotypes that we T1s living with diabetes for decades have to manage on a DAILY basis. Thanks.

      • Shalynn Carlo

        I’m twenty years old and was just diagnosed last December (12-1-12) when I went into DKA. I would love for a cure to come about. I want my “normal” life back. Find the cure and treat EVERYONE with T1D. Not just children….especially when you can become Diabetic at any age, not just as a child.

  • Laurie

    I volunteer to be on of the first to try this cure, when you figure it out! I’m a T1 also, 20 years. I think the best bet would be to use our own stem cells to “fix” the immunosuppression problem. That way, there would be no rejection and no need for other drugs.

  • Courtney Sams

    This is extremely uplifting to hear! A few questions I would ask (it might be too early to address these questions) are: 1. How much would it cost? 2. Would only children (under 18) be treated? 3. How is it done? Surgery, shots, pills? I am very excited to research this and keep tabs on how this is progressing! Thank you Dr. Fiorina for all the time you have put into the research for a cure.

  • Mahesh More

    Great news !!!
    Waiting for further updates on therapies.

    My wife has T1D from last two years and she is 31 yrs old. I hope the benefits will not be age specific.

  • A.P. Constantin

    As a health professional, let me put a small note of caution here. The paper in the January 2013 issue of Diabetes, cited as reporting the discovery, is actually on preventing rejection of transplanted islets in mice. How the PR office jumped from this to “root cause” is not clear to me. Sorry to pour cold water on this but this is not the first time a root cause or a radical cure for diabetes has been “discovered”.

    • Todd Beall

      Great point. I wondered when they said “root cause” in the article…

  • natsera

    I was going to comment on the extreme focus on children, but I see others have had the same reaction. I was diagnosed at age 43, and was definitely NOT a child! I’m now 65, and don’t expect to see a cure in my lifetime, but let’s talk about everyone with T1, not just children!

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