An amazing paper appeared today in The New England Journal of Medicine.
For many years, scientists have been trying to transplant pancreatic Beta cells to cure Type 1 Diabetes. The problem is that Type 1 is an autoimmune disease, and the patient’s immune system is primed to target the transplanted Beta cells. Most protocols that have been employed use high doses of powerful immunosuppressive drugs; these drugs have many risks and side effects.
In this paper, they use genetic methods to make the donor Beta cells “hypoimmune,” meaning they will not be detected or destroyed by the immune system. They used CRISPR to inactivate two genes that are required for a cell to be recognized and destroyed by the immune system, and they also engineered the cells to overexpress a gene called CD47 that signals the immune system to “don’t eat me.”
These genetically engineered Beta cells were transplanted into a 42-year-old man with a 37-year history of type 1 diabetes. After 12 weeks, the transplanted islet cells are still active, making insulin, and the patient no longer requires insulin injections. Sounds to me like a cure.
I read online that six-month patient follow-up results were presented at the 85th Annual American Diabetes Association (ADA) meeting. So still good after 6 months.
Of course, this is only one patient. But it is very promising. Importantly this study used “Allogeneic" Beta cells, meaning the Beta cells are genetically unrelated to the recipient. Thus, they could be used for any patient.
I feel like I’m one of the few who isn’t completely jaded on a “cure”. I’ve always believed it would happen in my lifetime. Yeah, I’ve heard the “five years away” for decades, too, but I knew that was said in ignorance when we barely even understood what diabetes was, let alone the mechanics. I knew we weren’t there yet, but that we could get there.
The first beta cell transplants were promising, but not earth shattering to me. Just felt like another stepping stone. Post Covid, especially mast cell activation and it’s long-covid symptoms, we’ve seen a lot of new research into autoimmune conditions… But this is the first time it’s really felt tangible. I’m finding myself really emotional about this one. It’s astounding, not just promising.
This is the first I’ve actually wondered what it would be like to not be consumed with this anymore? It’s such a big part of who I am after all this time.
Totally realistic, though, I feel like this is when the ten year timer starts.
There is really no point if we have to take immuno suppressants.
It’s like trading off one disease for another.
This new study is really promising and I think likely to be the path out of Type 1.
I was promised a cure for so many years, that I all but gave up on it.
I nearly went for it on an encapsulated trial for Vertex, but then COVID came and I got spooked taking anti rejection drugs.
After that whole thing, I’m staying away until I get get a transplant with no drugs
David, I heard about this beta cell transplant from a medical podcast…using stem cells to substitute for the deficient beta cells. The risk of rejection and use of stong immunosuppresent drugs was mentioned as limiting its use. Also the subjects had to have multiple hypoglycemic events and low glucose unawareness episodes to qualify for the stem cell transplant. Thank you for your thorough analysis of the study.
I heard an informed discussion on this on the Dr. Dawn podcast….there was much emphasis on this being used for Type 1s that have severe hypoglycemia unawareness. Also the anti-rejection drugs made it very unappealing for me.
Reading the summary (below): NO IMMUNOSUPPRESSION!
How much would I pay for this? A LOT!! I would like to see longer follow-up than 12 weeks, though.
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The need to suppress a patient’s immune system after the transplantation of allogeneic cells is associated with wide-ranging side effects. We report the outcomes of transplantation of genetically modified allogeneic donor islet cells into a man with long-standing type 1 diabetes. We used clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated protein 12b (Cas12b) editing and lentiviral transduction to genetically edit the cells to avoid rejection; the cells were then transplanted into the participant’s forearm muscle. He did not receive any immunosuppressive drugs and, at 12 weeks after transplantation, showed no immune response against the gene-edited cells. C-peptide measurements showed stable and glucose-responsive insulin secretion. A total of four adverse events occurred, none of which were serious or related to the study drug. (Funded by the Leona M. and Harry B. Helmsley Charitable Trust; EudraCT number, 2023-507988-19-00; ClinicalTrials.gov number, NCT06239636.)
Sana Biotechnology is the company behind the clinical study. The study publication coincides with a new public stock offering, a steady history of financial losses, and lawsuits by earlier investors. That’s just context…
Definitely a promising approach to follow in subsequent clinical trials.
