Can We Cure Type 1 Diabetes?

From everydayhealth.com 

There’s a cliché in the type 1 diabetes community that a cure has been “five years away” for as long as anyone can remember. For decades, patients have been told that researchers were on the verge of a miraculous breakthrough. It hasn’t come true yet.

Is there a cure for type 1 diabetes? The short answer is no. And even if an experimental cure were discovered tomorrow, it would almost certainly take much longer than five years before it became available to most people with type 1.

But there are still reasons to be optimistic. While it seems unlikely that type 1 diabetes will be solved in a single stroke of genius, in the past several decades researchers have made significant progress toward therapies that could one day free many patients of the need to use insulin.

What Does a ‘Cure’ Mean for Type 1 Diabetes?

Type 1 diabetes is an autoimmune disease in which the body’s immune response mistakenly attacks the islet cells in the pancreas that create insulin, a hormone that is absolutely critical to human life. 

For most, a cure for type 1 diabetes would mean a therapy that would restore the body’s ability to produce its own insulin. Someone who had been cured would achieve and maintain normal blood sugar levels without the need for insulin injections or ongoing diabetes management.

Camillo Ricordi, MD, director emeritus of the Diabetes Research Institute in Miami, goes a little bit further. He believes that a cure has to restore normal blood sugar levels “without antirejection drugs or any toxic interventions that may introduce other problems. You cannot replace diabetes with another disease.”

The past two decades have yielded tremendous progress on therapies that could possibly restore insulin independence, even if they do not reverse the autoimmunity that caused it in the first place. These therapies rely on pancreas and stem cell transplants. But because they still require immunosuppressive drug regimens to protect the transplanted cells, they are therefore arguably not true cures.

Pancreas Transplants

Some people who receive a new pancreas will no longer need to use insulin or check their blood sugar. Their type 1 diabetes has essentially gone away.

For many reasons, however, pancreas transplants are not a practical option for most people with type 1 diabetes:

• The recipient will need to take antirejection drugs for the rest of their life.
• Only a little more than half of recipients achieve true insulin independence; others will need to continue using insulin.
• • Transplantation surgery is intense, expensive, and potentially risky.
  • Donor pancreases are very rare.

  The bottom line is that pancreas transplants can be a more burdensome treatment option than simply continuing to use insulin.

  As a result, pancreas transplants are only rarely performed. Most of the time they are limited to people who are already receiving a kidney transplant for end-stage diabetic kidney disease, or for people with extreme management challenges, such as dangerous hypoglycaemia unawareness.

  Islet Cell Transplants

  In an islet cell transplant, only the insulin-producing islet cells are transplanted, rather than the entire pancreas. This procedure is less invasive than a pancreas transplant: Donated islet cells are processed and purified, then transported through a thin tube to the recipient’s liver.

  The transplant can have excellent results. Some lucky transplant recipients have enjoyed healthy blood sugar without the use of insulin for a decade or more.

  Islet cell transplants, however, are not always effective. They require antirejection medication, and some recipients will need two or three infusions, which further limits the availability of the surgery. 

  Until very recently, this therapy was not approved in the United States, and it will never be widely available due to the small number of viable donor pancreases.

  Lab-Grown Islet Cell Transplants

  Researchers have invented a solution for the scarcity of organ donors: It is now possible to grow human islet cells in a laboratory, using stem cells. That gives doctors a potentially limitless supply of healthy islet cells for transplantation.

  Lab-grown stem cells have only been utilized in experimental trials, so far; they are not yet available for regular patients. But the results have been encouraging. A full dose of a new lab-grown islet cell therapy named zimislecel has been tested in a dozen volunteers. Ten of them achieved full insulin independence after one year.

  This treatment, which could be manufactured on a vast scale, is perhaps the experimental therapy closest to being a practical cure for type 1 diabetes. But it still must pass through years of vigorous stage 3 testing, which will evaluate the treatment’s safety and efficacy in a larger number of volunteers. Even if it succeeds and is approved, we don’t yet know if zimislecel will become available for almost anyone with type 1 diabetes, or if it will be limited to people with a more distinct need.

  The Final Step: Avoiding Immunosuppression

  The last piece of the puzzle, says Dr. Ricordi, is devising a therapy that does not require the ongoing use of antirejection drugs. These medications, which are currently essential for protecting transplanted cells and organs, can cause heavy side effects, increase the risk of infections, contribute to long-term health issues, and even become toxic to the transplanted cells themselves. For some patients, an immunosuppression regiment may be more trouble than it’s worth.

  “The ultimate goal is to do these transplants without immunosuppression,” says Ricordi.

  Some of the most advanced diabetes research in the world is now bent on the problem of how to protect or hide islet cells from the immune system. Today it is not at all clear how this problem will be solved, and biotechnology firms are trying many different approaches. Potential avenues include:

  • Gene-editing techniques that can hide transplanted islet cells from the immune system
  • Physical barriers that encapsulate islet cells, allowing glucose and insulin to flow freely while blocking immune cells
  • Immunosuppressive microgels that can be mixed with islet cells, preventing the need for chronic antirejection drug use
  • Nanocarriers that can deliver small precise amounts of immunosuppressive drugs exactly where they’re needed

  Most of these technologies are still early in development, and some earlier efforts have failed. One of the most promising inventions, a physical pouch that shields lab-grown islet cells, was recently discontinued due to poor results.

  If general immunosuppression is ultimately necessary, it may also be possible to vastly improve on the available antirejection drugs. Superior options could reduce side effects and enhance islet cell function rather than diminish it.

  Islet Cell Regeneration

  Transplantation isn’t necessarily the only path toward a cure.

  Other researchers are exploring therapies that aim to regenerate the body’s natural capacity to produce insulin. The pancreas of an adult with type 1 diabetes may still contain progenitor cells that can be instructed to turn into insulin-producing beta cells. Alternatively, beta cells can possibly duplicate themselves, which could allow a non-invasive therapy to cause even a tiny amount of beta cells to proliferate.

  These therapies would still require some other drug or technique to prevent the autoimmune attack from destroying or inactivating newly created beta cells. But Ricordi believes that investigating many different avenues at once is the approach most likely to result in success: “I believe in a combination strategy. I’m not sure there will ever be a silver bullet that will be 100 percent successful for everybody.”

  Timeline and Cost

  Ricordi has worked at the forefront of diabetes research for decades. He believes that we could be only years away from experimental proof of a real type 1 diabetes cure: one that can restore insulin production and hide the transplanted or rejuvenated islet cells from the immune system.

  But even in that optimistic scenario, there is no telling how many years it would take to get a cure out of the lab and into the bodies of people with diabetes. Ricordi cautions that even after a true cure is confirmed under experimental conditions, “it will take five years to follow up on the initial group.” Then it will take even longer to scale up and make the therapy widely available.

  Even after FDA approval, such a cure could be limited to only a tiny subset of people with the condition. It may be extraordinarily expensive, too. “Advanced cell therapies can cost hundreds of thousands of dollars,” Ricordi says.

  While the progress we’ve made toward a cure is exciting, it wouldn’t be wise to expect your own type 1 diabetes to be cured at any point in the foreseeable future. “We don’t want to create false hope,” Ricordi says.

  Automated Insulin Delivery Systems

  Although an insulin pump will never be a true cure for diabetes, some people hope that this technology can become so advanced that it will act almost as if it were a cure, removing almost all of the worries and burdens of people with type 1 diabetes. A theoretically perfect insulin pump system — one that could keep your blood sugar in range no matter what food or exercise decisions you made — would alleviate a massive amount of the cognitive and emotional burden of living with the disease.

  Automated insulin delivery (AID) systems combine a continuous glucose monitor (CGM) and an insulin pump so that they communicate with each other. A computer-controlled algorithm, which might reside in a smartphone or on the pump itself, decides exactly how much insulin you need, adjusting the delivery rate constantly around the clock.

  The AID systems of today can significantly improve quality of life, reducing diabetes distress and allowing people to feel freer in their food and exercise choices. But they aren’t yet a cure: Even if you ignore the cost and hassle of these wearable devices, users still need to manually dose insulin for meals, and still need to ingest sugar to fight off hypoglycaemia. 

  But in the future, we may have AID systems that work so quickly that patients will no longer need to count their carbs. It’s possible to imagine a pump system so good that it lets you forget about your diabetes, at least for a few days at a time.

  The Takeaway

  • Today, there is no cure for type 1 diabetes.
  • Pancreas and islet cell transplants can, in some cases, remove the need for insulin therapy. But these therapies are not widely available and still require the lifelong use of immunosuppressive drugs.
  • Automated insulin delivery systems and continuous glucose monitoring greatly aid in diabetes management and improve quality of life, but they are not a cure.
  • Researchers have made impressive advances toward a type 1 diabetes cure, and the condition is easier to manage than ever. But even in the most optimistic scenario, a new diabetes cure would take many years to become available.
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  • https://www.everydayhealth.com/diabetes/can-we-cure-type-1-diabetes/