How close are we to a cure for type 1 diabetes? Nobody is better positioned to know than Camillo Ricordi, MD, director emeritus of Miami’s Diabetes Research Institute.
The diabetes community is understandably skeptical of experts promising that a cure will be discovered in the near future — we’ve been hearing that for decades. But the truth is that researchers have made real (if slow) progress, and any number of experiments happening today could provide the key to the holy grail of diabetes research.
Dr. Ricordi performed much of the foundational work to bring us to where we are today. Now, he has a unique perch at the Diabetes Research Institute (DRI), helping to guide some of the most exciting clinical trials in the diabetes world. One such trial is almost certain to become the most eagerly-anticipated experiment in the diabetes world: Vertex Pharmaceutical’s new test of lab-grown islet cells that will be physically shielded from the immune system.
The science is very exciting, but the reality of implementing a cure could be depressing. Though Ricordi believes that we could be only years away from experimental proof of a real type 1 diabetes cure, even this most optimistic scenario is fraught with regulatory and economic challenges. There’s no telling how many years it would take to get a cure out of the lab and into the bodies of people with diabetes — nor how much it would cost.
Obstacles aside, Ricordi and the DRI remain entirely devoted to finding a cure for type 1 diabetes. Here’s what he had to tell us.
What’s the Definition of a Type 1 Diabetes Cure?
There are many competing definitions of a “cure” for type 1 diabetes.
Some may say, for example, that a pancreas transplant cures T1D — after all, in some cases it can fully restore healthy insulin production, allowing patients to eat whatever they want without using insulin. But it comes at a severe cost, an oppressive regimen of immunosuppressive drugs with heavy side effects, and a high probability of eventual failure. Meanwhile, some biotech firms concentrate on a “functional cure,” a combination of medicine and technology that will allow people with T1D to live completely normal lives without changing the underlying physiology of the disease.
Ricordi is hoping for something better, a true cure, something that wipes out type 1 diabetes and guarantees that it will never come back:
“My definition of a cure is the ability to replace the biologic endocrine function of the pancreas that has been selectively destroyed by an autoimmune response, and to do so without antirejection drugs or any toxic interventions that may introduce other problems. You cannot replace diabetes with another disease.”
“But my definition goes beyond that, because my motto is ‘there is no cure without prevention.’ The moment you find a successful cell therapy, then you have to work on preventing disease recurrence, and preventing the accelerated aging and chronic complications that are associated with the disease.”
“The [therapy] you’re introducing to prevent the recurrence of the disease may be able to prevent the disease in the first place. It’s a 360-degree intervention: primary prevention, cure of those diagnosed, and prevention of disease recurrence, accelerated aging, and other complications.”
How Close Are We to a Cure?
Ricordi is well aware that people in the diabetes community are sick and tired of hearing that a cure is “five years away.” Way back in 1984, Ricordi says, his colleagues shoved him onto a plane headed to America from Milan, telling him that “they found a cure with islet transplantation and you need to bring it back to Europe.” But there were still decades of work to do.
In 1988, Ricordi developed an automated method of islet isolation that would help make islet transplants feasible. In 1990, he helped show that islet transplantation could revive insulin production in people without a pancreas. In 1999, the Edmonton protocol did the same for people with autoimmune type 1 diabetes. In 2021, Vertex had success with lab-grown islet cells, offering a new possibility of a limitless supply of healthy islets for transplantation.
“It’s been a long path, but now that we’re tackling the last part: tolerance induction and disease recurrence. It makes me very hopeful… The development of a proof of concept of a cure could be in less than five years, or could be more than fifteen, depending on a lot of factors.”
Ricordi cautions that even if a true cure is confirmed under experimental conditions within the next several years, “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.
“The timing of implementation for all people with type 1 diabetes is another question. We don’t want to create false hope.”
But he does offer a defense for times in the past when his colleagues have perhaps overzealously announced how close we were to a cure:
“I don’t think it was just hype, because if you don’t believe that one of these trials or protocols or strategies might be the one that can make a difference, why are you doing it? I think it’s important to keep our team’s focus and intensity on a cure, as if it’s around the next corner, but with the awareness that it could take another decade or more.”
The Problem with Immunosuppression
In June, we learned that two early Vertex patients are now completely insulin-independent. “It’s been an incredible milestone to show that stem cell-derived islets can reverse diabetes and induce long-term insulin independence,” Ricordi says.
But Vertex’s first successful T1D therapy, a transplant of lab-grown islet cells, still requires the use of immunosuppressive drugs. These drugs carry serious risks, including cancer and life-threatening infections.
It gets even worse: Prograf (tacrolimus), the major antirejection drug used in islet transplants, is actually toxic to the cells that it’s protecting. In some cases, the drug can even cause diabetes. This toxicity helps explain why, in the long term, most islet transplants eventually fail.
“The ultimate goal is to do these transplants without immunosuppression,” says Ricordi.
The Best Chance for a Cure: VX-264
The most exciting research happening at the Diabetes Research Institute right now will try to do exactly that. Ricordi is in the process of helping to activate the first human trial of Vertex’s newest therapy, VX-264, which encapsulates transplanted islet cells, shielding them from the immune system with a physical barrier. The device, Ricordi says, is the result of “amazing engineering and nanotechnology.” The DRI will be one of several sites in multiple countries to carry out this potentially game-changing work.
The Diabetes Research Institute is currently enrolling for the VX-264 trial, trying to find one or more brave and potentially very lucky patients willing to take a gamble on what could be a milestone in the race for a diabetes cure.
If all goes according to plan, the first patient will be implanted soon. They will receive a partial dose of islet cells, and the initial results will be primarily assessed for safety, not efficacy. The trial is predicted to end in May 2026, but we’ll have early results before then.
The Diabetes Research Institute
Other Exciting Trials
The DRI is not, by any means, putting all its eggs in one basket. Vertex is only just one approach, and it hasn’t succeeded yet. Even if it does, it may not be the right therapy for everyone with type 1 diabetes.
“Vertex for sure has the pole position. But you don’t know who will win until the race is complete,” Ricordi says. “I believe in combination strategy. I’m not sure there will ever be a single bullet that will be 100 percent successful for everybody.”
Ricordi highlighted two other especially exciting trials that the DRI is helping with. Both focus on what Ricordi called the “last part” of the cure puzzle: immunosuppression.
The first is the dream of a biotech startup named iTolerance, which is working on a microgel that could be mixed with islet cells prior to transplant. This substance can cause the T-cells that would attack the new islets to self-destruct. It can also retrain the immune system to privilege the area, allowing the islet cells to do their work unmolested. The result is local immune tolerance, “tricking the immune system to accept the transplanted organ as if it were its own cells.” And it might all work without any general immunosuppression.
“I’m very happy that we also have non-device based approaches for tolerance induction,” Ricordi says. At the moment, there’s no telling if physical immune system barriers like Vertex’s will work, either initially or in the long term. ViaCyte, a former Vertex competitor, evidently saw its experiments in physical encapsulation end in failure.
Ricordi is similarly excited about trials testing an anti-rejection drug that could be significantly superior to Prograf, a “costimulatory blocking molecule” developed by Eledon Pharmaceuticals. This drug, unlike Prograf, is not at all diabetogenic — Ricordi says that early studies have indicated it will “triple the insulin production from transplanted islets.”
Finding an improvement over Prograf wouldn’t exactly constitute a cure, but it would be “an incredible step,” says Ricordi. It could make islet transplants far safer and longer-lasting, which would likely make the procedure a viable option for many more patients. “Maybe this could be a key component to a tolerance-induction protocol to eventually get to complete drug-free islet transplantation.”
There are, of course, other trials going on around the world that the Diabetes Research Institute isn’t involved in. DiogenX, for example, is working on a synthetic protein that could cause the pancreas to grow new beta cells. ViaCyte — which was purchased by Vertex — laid the groundwork for islet cells that have been gene-edited to evade the immune system, another avenue that Vertex can explore.
Some of these various strategies could end up combining to form an eventual cure. Ricordi is somewhat doubtful, for example, about islet cells that have been gene-edited for “complete stealth.” But he thinks that gene editing with a lighter touch could play “a big role down the line. If you make the cells less immunogenic, maybe it’s easier to induce immune tolerance to those islets.”
How Much Will a Type 1 Diabetes Cure Cost?
“Everybody asks when we’ll have a cure, but I’m also questioning who will be able to afford it. We need to keep things as non-profit as possible.”
In Europe, Ricordi explains, the government approves medicines and prices simultaneously. “But in the United States, once the FDA approves a drug, it’s the Wild West.”
“Advanced cell therapies can cost hundreds of thousands of dollars. I’m wondering if it’s economically sustainable.”
Although Ricordi works intimately with Vertex on testing therapies, he is completely segregated from the team that will decide how to price any approved therapy. Vertex has spent well over a billion dollars acquiring and developing its experimental therapies, and it will have a powerful incentive to charge heavily for a therapy that would be received as a miracle.
Would Vertex charge an arm and a leg for a type 1 diabetes cure? Ricordi can only say, “I hope not, but I don’t know.”
Choosing the DRI
Commitment to the cause is what led Ricordi to Miami in the first place. In the early 90s, Ricordi found himself heavily recruited by multiple institutions, but turned down big dogs like Harvard in favor of the Diabetes Research Institute.
“I chose DRI because it offered something unique: a mission that allowed us to stay focused on finding a cure for type 1 diabetes. It’s been my lifetime professional mission since my little cousin was diagnosed with type 1, back when I graduated from medical school.”
Dr. Ricordi has recently stepped down as scientific director, though he remains heavily involved in the work that goes on. A new director, Matthias von Herrath, MD, has been named. Dr. von Herrath, a world expert on diabetes and immunology, will not change the organization’s mission.
“This building has to remain dedicated to finding a cure for diabetes.”
Ricordi has shown this commitment throughout his career. When he invented his new process to isolate islet cells — a technique that is now used for islet transplants across the world — he released all of his intellectual property, so as to allow it to spread as quickly as possible. When scientists join the Diabetes Research Institute, they’re asked to make a similar commitment:
“If you work at DRI, you have to pledge that you’re not here to keep secrets. You have to be collaborative, sharing, and helping everyone else. We help anyone throughout the world who can help us get to a cure in the fastest, most efficient way possible.”