Breakthrough T1D CEO Aaron Kowalski, Ph.D., weighs in on the exciting, recent news surrounding stem cell-derived beta cell replacement therapies, now in human clinical trials, and as reported  in The New York Times on Saturday, November 27. 

As we approach the end of 2021, I am elated by the incredible progress we’ve seen in T1D research and development. On Saturday, The New York Times reported on a clinical trial that is currently being conducted by the company Vertex and the news has generated significant interest in the community and has elicited a spectrum of emotions—from joy and hope, to skepticism and doubt.

Given that this area of research is a top priority for us at Breakthrough T1D, and that we funded and advocated for this work and many more of the exciting advancements happening in T1D today, I thought I would weigh in with my perspective.

A little bit about me (for those of you who may not know my story): I’ve been CEO at Breakthrough T1D for about 2.5 years now and prior to taking on the role of CEO, I spent many years as a member and then the leader of the scientific team (my background being molecular genetics). While I’ve worked professionally on diabetes a long time, my family has been impacted by the disease much longer—more than 40 years. My brother Stephen was diagnosed with T1D at the age of 3 in 1977 and started on two shots of animal insulin a day and urine glucose testing. I was diagnosed at 13 in 1984, when color-based glucose testing and three shots of animal (cow-pig) insulin a day was the norm.

Today we are fortunate to be healthy and benefitting tremendously from the T1D technologies Breakthrough T1D played a seminal role in advancing. That said, my goal at Breakthrough T1D is the same as the founding families that formed this great organization—cures for T1D! This is why these recent reports are so important.

This past Saturday’s The New York Times reported on the experience of the first patient to be implanted with Vertex’s stem cell-derived islets, Mr. Brian Shelton, in a clinical trial run by the company Vertex. The New York Times reports, “Now his body automatically controls its insulin and blood sugar levels,” and that, “Mr. Shelton, now 64, may be the first person cured of the disease.” This amazing anecdote was reported by Vertex in a press release on Monday, October 18, and Breakthrough T1D made a statement regarding our excitement from this first report.

Here I’d like to express my excitement as well and provide some additional context. Is Mr. Shelton the first person to be “cured” of type 1 diabetes? No—he is not. But is this truly a sign of progress? Yes it is—and it’s one of several potential cures in human clinical trials, with support from Breakthrough T1D and all of you.

The Backstory: Islet Cell Transplantation

There have been thousands of people with T1D who have had their blood sugars normalized by receiving islet transplantations and in some cases whole pancreas transplants. These are fields of research that Breakthrough T1D invested in heavily going back to the 1980s and culminating in 1999 with what today is known as “The Edmonton Protocol.”

Led by James Shapiro, M.D., Ph.D., and an incredible multi-disciplinary team, people with T1D were infused with cells from organ donors and with a less toxic immunosuppression than was used previously (to prevent rejection of the islets). The results are incredible—restoration of normal blood sugars and insulin production for a decade on average. The challenge with this approach was two-fold: The need for organ donation for islets and the need for chronic immunosuppression. Breakthrough T1D has been working on solving each of these challenges (which are big challenges!) since the advent of islet transplantation.

Challenge #1: The need for an unlimited number of cells

The math is simple—to develop cures for everyone with T1D, organ donation is not sufficient. There are far too few pancreas organ donations each year to help the 1.6 million people with T1D in the United States and many millions more globally. While islet cell transplantation provided proof of concept, we knew we needed an additional source of insulin-producing cells. To solve this problem, Breakthrough T1D became an early pioneer in the field of stem cell research—funding and advocating for the ethical use of stem cells to cure diseases.

Breakthrough T1D strongly advocated on Capitol Hill for years to ensure research could proceed and funded research grants in the United States and across the globe to advance the science focused on the process of transforming stem cells into insulin-producing beta cells (and the other hormone producing cells of the islet). Doug Melton, Ph.D., who is highlighted in this The New York Times article, was an early scientific leader in the field. Breakthrough T1D began support of Dr. Melton’s work in 2000 and our funding continues today. When Dr. Melton formed his company, Semma, the Breakthrough T1D T1D Fund provided crucial investment to move this research into product development, which led, several years later, into it being acquired by Vertex. Breakthrough T1D has also supported many other groups who have developed insulin-producing cells from stem cells—funding hundreds of researchers around the world for the past 20 years and supporting over 40 groups and $80 million of currently active research globally.

Challenge #2: The need for immunosuppression

Islet transplantation requires a lifetime of immunosuppression so that the transplanted cells are not rejected. In fact, rejection of beta cells is driven by two challenges: The first is that the cells are from a donor and just like any other transplant, without immunosuppression, the cells will be rejected. Second, the person with diabetes still has autoimmunity and our bodies will attack beta cells. We call these alloimmunity and autoimmunity, respectively. Breakthrough T1D has invested heavily in solving these challenges, launching a Beta Cell Consortium in 2013 which is supporting research by multiple teams focused on four primary fronts:

  • Macroencapsulation of the cells: Placing a group of cells in a “device” that physically protects them;
  • Microencapsulation of the cells, also physically protecting the cells, but at the cellular level;
  • Gene editing (using CRISPR or other methods to modify the cells so that they are “invisible” to the immune system); and
  • Immunologic approaches that “teach” the immune system to not attack the new insulin-producing cells or provide “local” immune protection to the transplanted cells.

The Latest Progress and Why it Matters

OK, that’s a lot of background and context—but, it’s important to understand why this report is so noteworthy, what else is happening in the field, and what is coming next. With that, I’d like to address a number of the questions that I’ve received, and seen posed in the diabetes online community:

1. Is this a big deal? I thought we’ve been able to do this since islet transplantation.

This is a really big deal!! Yes, islet transplantation has shown that we can restore normal blood sugar levels with transplanted cells, but as I’ve described above, we don’t have enough islets. Stem cell-derived islets could provide an unlimited source. This would allow (theoretically) everyone with T1D to have cells. It’s been 20 plus years of research that has taken us to a place where stem cell-derived islets could be tested in people. The Vertex report is an awesome step forward. I should also note that Breakthrough T1D (including Breakthrough T1D’s T1D Fund) believes that competition drives innovation and that “multiple shots on goal” are a good thing.

It’s important to note that JDRF-supported firms ViaCyte and Sernova have also recently reported insulin-production in their human trials of stem cell-derived T1D therapies. In 2019, Sernova showed in its Breakthrough T1D-funded clinical trial that its cell replacement therapy, the Cell Pouch System™, can produce insulin in people with T1D.

That same year, ViaCyte, a beta cell replacement company long supported by Breakthrough T1D, showed—for the first time ever—that its PEC-Encap therapy helps people with T1D produce insulin again. Last month, ViaCyte and CRISPR Therapeutics announced another exciting first: Gene-editing for T1D. By the end of the year, they will start a clinical trial of VCTX210, a gene-edited stem cell replacement therapy for this disease.  

And, the T1D Fund has several important investments including Seraxis, Diagon, and eGenesis, all of whom are working on beta cell replacement technologies.

2. Why is Vertex reporting just the data from one person? Shouldn’t they have waited until the trial was complete?

This is data from just one person, and, as a scientist, I know it’s critical for us to see the data from the entire group of people who receive these cell transplants. The field will not move forward until many more people participate in these trials. That said, it is a significant finding that these cells are making insulin and driving clinical benefit. This finding will help us begin to plan the next stage of clinical trials and assess the benefit/risk of this potential therapy, including paving regulatory and health policy pathways that are key priorities of Breakthrough T1D.   

3. But Mr. Shelton is still taking immunosuppressants. Isn’t that like trading one problem for another?

Mr. Shelton is indeed on immunosuppressants in this trial. That said, this is an important step. There are a number of circumstances in which the benefit/risk of a therapy that includes  immunosuppression could be positive. For example, there are many people with T1D who are already taking immunosuppressants due to having had a kidney transplant. A therapy like this could take away their diabetes without adding new risks from immune suppression. That could be a HUGE step forward for many people with T1D. At the same time, many people with T1D face significant risks from the disease every day. Given the improved safety profile of anti-rejection drugs, I’d venture that for a number of people the tradeoff would be a positive one.

4. Is Breakthrough T1D jumping on the bandwagon? Is Breakthrough T1D really committed to a cure?

For over 20 years beta cell therapy has been a major area of focus for us and we’ve been the leading organization focused on curing T1D since two families founded our organization to develop cures for their sons. Breakthrough T1D has been a leader in stem cell research since the beginning and has funded over $150 million since 2000. In this case, Breakthrough T1D funded Dr. Melton back in 2000 and continues to do so today. Our T1D Fund invested in Dr. Melton’s company Semma and we are currently working with Vertex to accelerate the pathway to regulatory approval and health care coverage. While I’m proud of my work as a scientist at Breakthrough T1D on artificial pancreas systems (and my brother and I currently wear artificial pancreas systems that are derived from Breakthrough T1D-supported work), more than anything else I want to take off my diabetes devices and achieve what our founders set out to do—find cures for T1D.

5. What’s next? When might I or my loved one benefit from this work?

JDRF’s mission is “Improving lives today and tomorrow by accelerating life-changing breakthroughs to cure, prevent, and treat T1D and its complications.” Of course, there would be nothing more life-changing than taking off our pumps, putting down our insulin pens, and making our own insulin again. I dream about that every day, for my brother Steve and me, and for everyone impacted by T1D. Breakthrough T1D will do all that we can to see this work move forward as fast as possible. We will continue to fund millions of dollars in research, our T1D Fund will continue to invest in companies moving forward in this space, our regulatory team will continue to work with FDA and regulators around the world on pathways to product approvals, and our health policy team will continue to work on ensuring that when these products are approved, they are affordable and accessible to everyone with T1D. Your ongoing support for this mission critical work is essential for our success.

6. I heard this before and just can’t get my hopes up too high. Has Breakthrough T1D given up on better treatments and prevention of T1D?

I realize that there is sentiment out there that cures are “always right around the corner.” I appreciate this but remember that science is moving forward and ultimately the data are the data. These approaches are now being tested in people and the data are very compelling. Moreover, the approaches have moved from academia to formal research and development programs. There is work to be done, but I firmly believe this isn’t a matter of if stem-cell transplants will be available to the T1D community, it’s only a matter of when. The more research and advocacy we support—the faster it will happen.

Breakthrough T1D will continue to support work on better treatments and prevention as well. We need our T1D community to be healthy when cures arrive and we need to stop T1D from happening in the next generation. Tremendous progress is being made on both of these fronts as well.

  • We have multiple automated insulin-delivery systems on the market and more coming in the near future. They continue to get smaller, more integrated, and drive better control. Breakthrough T1D also continues to invest in glucose-responsive insulins and other approaches to lower blood sugar beyond insulin.
  • We’ve also made great strides in prevention. The first drug to delay T1D—teplizumab—received FDA advisory committee recommendation for approval this past summer. Breakthrough T1D and our T1D Fund continue to make investments that aim to restore immune balance in T1D, which will be critical in stopping the development of the disease and to provide further curative approaches beyond cell replacements.

More Optimistic Than Ever

Let’s come full circle. The recent report in The New York Times has generated great excitement and many questions. I welcome both of these responses. I’m thrilled that Vertex is moving the work from Dr. Melton and Semma into the clinic and toward a product. This is huge. I’m thrilled that companies such as ViaCyte, Sernova, and others are racing to get there as well. I’m proud that Breakthrough T1D has played a pivotal role in this field moving forward and I’m more committed than ever that we will do everything we can to accelerate these life-changing breakthroughs to everyone with T1D.