The recent news about successful clinical trials in islet cell therapies for type 1 diabetes cures is very exciting. But the science behind it can be confusing. Breakthrough T1D is here to answer all of your questions about islet cells, from the research lab to real-world treatments.
What are islet cells?
Islet cells are a group of cells in the pancreas that release hormones to regulate blood sugar. Beta cells are a type of islet cell that make insulin. In people with type 1 diabetes (T1D), the autoimmune system destroys the beta cells in the pancreas, which produce insulin.
What is islet cell therapy?
Islet cell therapies replace destroyed islet cells with external insulin-producing cells and protect them so that they can function for a very long time.
Is islet cell therapy a cure for type 1 diabetes?
The answer is: It could be.
Adults around the world who have received islet cell transplants are coming off external insulin, lasting from months to years. But for newer, more advanced islet cell therapies, we are still doing clinical trials and don’t yet know how these cells will work long-term.
Right now, islet cell therapies as potential cures for type 1 diabetes are limited to adults with severe T1D who have a lot of trouble managing their condition. Even more, adults who are eligible to receive islet cell therapies need to take lifelong immunosuppressants, which, depending on other health considerations, may not be the right decision for everyone.
To make islet cell therapies available to everyone with T1D who may want them, Breakthrough T1D’s end goal is to manufacture islet cells on a large scale and safely put them inside the body of every person with T1D to replace the cells that were lost without the use of immunosuppressants. This would effectively cure type 1 diabetes.
Are there any islet cell therapies available right now?
In Europe and Canada, islet cell therapies using islet cells from deceased donors have been successfully used to treat people with T1D for years.
In the United States, there is currently one islet cell therapy approved for T1D as of 2023 called Lantidra®, which is also derived from deceased donors. Lantidra and other islet cell therapies used around the world are intended for adults with T1D who experience:
- Severe hypoglycemia (dangerous low blood sugar)
- Hypoglycemia unawareness (the inability to sense when blood sugar is dropping)
These individuals often cannot safely manage their blood glucose levels with the standard therapies used to manage T1D.
Other islet cell therapies are still in clinical trials. Adults with T1D who are interested in participating in these clinical trials generally must meet the same eligibility requirements: severe hypoglycemia and hypoglycemia unawareness.
What are deceased donor islet cells?
Deceased donor islet cells come from the pancreases of deceased donors. It can take up to three pancreases to get enough islet cells for one transplant. Deceased donor islet cells are in limited supply, and there aren’t enough for everyone with T1D who may want them. This is similar to a kidney or liver transplant—there aren’t enough organs for everyone who needs them.
What are manufactured islet cells?
Thanks to years of support from Breakthrough T1D and others, scientists can manufacture islet cells in a laboratory by using specific protocols to turn precursor cells into insulin-producing cells. Manufactured islet cells can be made in large quantities and are the only solution to making sure there are enough islet cells for everyone with T1D who may want them.
How are islet cells transplanted?
Islet cell transplantation is a procedure in which insulin-producing islet cells (from either deceased donors or a manufactured source) are transplanted into a person living with T1D. Once transplanted, these cells can begin producing insulin in response to blood glucose levels.
Lantidra, the only approved donor-derived islet cell therapy for T1D in the U.S., is transplanted as a single infusion into a vein in the liver. Other islet cell therapies in clinical trials are testing different transplantation sites around the body, such as in the forearm muscles, in a small device underneath the skin, or within the abdominal wall. The goal is to figure out which transplant sites allow the cells to have the greatest chance of survival.
Recipients of Lantidra—and most other donor-derived and manufactured islet cell therapies in clinical trials—must take immunosuppressives to prevent the body from rejecting the transplanted cells. However, researchers are testing new ways to protect islet cells without immunosuppressants.
What is immunosuppression?
Immunosuppression uses drugs to reduce the effectiveness of your immune system. It is required to prevent your body from rejecting a transplant.
A person who receives a transplant of any kind will almost always need to take immunosuppressants for the rest of their lives. Immunosuppressants help keep transplanted organs, tissues, and cells alive. However, they can come with side effects and may make individuals more susceptible to infections and cancers. For those who are eligible to receive an islet cell transplant, it is up to individuals and their care teams to determine if the benefits of receiving a transplant outweigh the risks of lifelong immunosuppression.
Why do current cell therapies require immunosuppression?
Most islet cell therapies—including Lantidra and those in clinical trials—require immunosuppression. This is because the source of the islet cells comes from somewhere other than your own body. Your body views the transplanted cells as “foreign,” meaning the immune system will activate and reject the transplant, and the islet cells will die. To prevent this from happening, immunosuppressants can dampen your immune system so that it doesn’t attack the transplanted cells.
Researchers are finding new ways to make immunosuppression milder or remove the need for immunosuppression altogether. Some of these approaches are already in clinical trials.
Why is there so much talk about clinical trials and T1D?
Without clinical trials, we would never know if new therapies developed by scientists in the lab could make a difference in people’s lives. This is where the T1D community comes in! By volunteering to participate in clinical trials, you become uniquely positioned to help drive biomedical research forward. Moreover, by participating, you help not only yourself, but everyone with T1D.
Why are there such specific eligibility requirements for cell therapy clinical trials?
Clinical trials can come with both risks and benefits. The potential benefit would be the islet cell therapy working, meaning the transplanted islets survive and make insulin. The potential risks include side effects from the transplant procedure, chronic immunosuppression, and more.
Right now, these trials are limited to adults with the most difficultly managing their T1D because the potential benefits outweigh the risks. The adults eligible to participate in these trials will help researchers gather more evidence about the safety and efficacy of islet cell replacement therapies.
Until researchers have more data on the safety and efficacy of islet cell therapies, children are not yet eligible for these trials to protect them from the potential risks. Future clinical trials may be available to children and other populations of adults with T1D, but we are not there yet.
Where can I find cell therapy clinical trials I’m eligible for?
Breakthrough T1D has an easy-to-use tool called the Clinical Trials Connection, which asks users simple questions—about where they live, the distance they can travel, and other characteristics—to match them with trials for which they are eligible.
Here are some currently recruiting trials in cell therapies in the U.S.:
| Clinical Trial Name | Immunosuppression Required? | Participation Criteria |
|---|---|---|
| A Safety, Tolerability, and Efficacy Study of VX-880 in Participants With Type 1 Diabetes | Yes | Ages: 18 to 65 Years Living with Insulin-Dependent T1D: More than 5 Other Criteria: At least two episodes of documented severe hypoglycemia in the 12 months prior to enrollment Consistent use of a CGM for at least 3 months before screening |
| An Efficacy, Safety, and Tolerability Study of VX-880 in Participants With Type 1 Diabetes With a Kidney Transplant | Yes | Ages: 18 to 65 Years Living with Insulin-Dependent T1D: More than 5 Other Criteria: Taking a stable immunosuppression regimen of tacrolimus and mycophenolate mofetil, mycophenolate sodium, or sirolimus for at least 4 weeks Consistent use of CGM for at least 4 weeks before screening and willingness to use CGM for the duration of the study |
| Safety, Tolerability, and Efficacy of Immunomodulation With A Monoclonal Antibody Against CD40L in Combination With Transplanted Islet Cells in Adults With Brittle Type 1 Diabetes Mellitus (T1D) (Tegoprubart) | Yes | Ages: 18 to 65 Years Living with Insulin-Dependent T1D: More than 5 HbA1c Level: 6.5% to 9.5% Other Criteria: At least 3 unexplained severe hypoglycemic episodes not secondary to a missed meal or dosing error, in the 12 months prior Impaired awareness of hypoglycemia |
| Breakthrough – T1DM and Chronic Kidney Disease | Yes | Ages: 18 to 70 Years Living with Insulin-Dependent T1D: More than 5 HbA1c Level: 6.5% to 9.5% Other Criteria: Chronic kidney disease stage 1, 2 or 3a |
| A Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus | No | Ages: 35 to 65 Years Living with Insulin-Dependent T1D: More than 5 HbA1c Level: Over 9.0% Other Criteria: Unable to achieve adequate control of T1D using a closed-loop systems for at least 6 months prior to enrollment At least one episode of severe hypoglycemia in the 12 months prior to study consent |
| Improving Islet Transplantation Outcomes With Gastrin for Type 1 Diabetes | Yes | Ages: 18 to 68 Years Living with Insulin-Dependent T1D: More than 5 Other Criteria: Unstable blood glucose characterized by frequent hypoglycemia and/or hypoglycemic unawareness and/or one or more hospital visits for DKA in the 12 months preceding enrollment |
| Islet Transplantation in Type 1 Diabetic Kidney Allograft | Yes | Ages: 18 to 68 Years Living with Insulin-Dependent T1D: More than 5 Other Criteria: Kidney transplant 3 or more months ago and taking appropriate calcineurin inhibitor (CNI)-based maintenance immunosuppression |
| Pancreatic Islet Transplantation Into the Anterior Chamber of the Eye | Yes (localized eye drops) | Ages: 18 to 75 Other Criteria: At least one eye with extensive loss of vision from hand motion to no light perception Phakic or pseudophakic with a stable intraocular lens in the blind eye Normal cornea with good visualization of the anterior segment Normal anterior segment anatomy including the iris bed |
| Islet Transplantation With Recipient T-Reg Cells or Deceased Donor Vertebral Bone Marrow Therapy | Yes | Ages: 18 to 75 Years Living with Insulin-Dependent T1D: More than 5 Other Criteria: Involvement in intensive diabetes management defined as self-monitoring of glucose values no less than a mean of three times each day averaged over each week and by the administration of three or more insulin injections each day or insulin pump therapy. At least two episodes of severe hypoglycemia in the 12 months prior to study enrollment Reduced awareness of hypoglycemia |
Everyone says a cure is 5-10 years away. Why does progress seem to be so slow for T1D advancements?
First, clinical trials can take quite a long time. It can be difficult to find people with T1D who are eligible and willing to participate. Also, people who are receiving a new therapy or treatment often need to be monitored for years to understand long-term safety and efficacy.
Second, science is often complex and unpredictable. Research and clinical trials don’t always turn out the way we hope they will. And we can’t always predict how long research will take. But, all data is good data! Researchers learn from clinical trials to help think about the best way to approach future studies.
Does fundraising for Breakthrough T1D helping fund research in cell therapies?
As the leading global T1D research and advocacy organization, Breakthrough T1D is currently funding over $450 million in research in 24 countries. Everything we do is focused on making cures happen for everyone facing T1D, sooner.
Without continuous support from the T1D community, we would never have gotten this far.
Breakthrough T1D looks forward to a future where manufactured islet therapies are a reality for everyone with T1D, and we will not stop until we get there.
Will cell therapies ever become available for everyone living with T1D?
In the coming years, it’s likely that first-generation manufactured islet therapies will be available to people with T1D with severe hypoglycemia unawareness and will require broad immunosuppression. Later, advancements in cell survival and immune protection—combined with the discovery of more tolerable immune suppression approaches—will open the doors for more people with T1D to access these life-changing therapies.
Project ACT
Scientific progress takes time, money, and effort. To accelerate islet replacement therapies faster than ever, Breakthrough T1D launched Project ACT (Accelerate Cell Therapies) to simultaneously advance research, development, regulatory policies, access, and adoption of manufactured islet therapies that do not require broad immunosuppression.
By Sandy Vogt, Ph.D. and Kara Sweet
