A truly groundbreaking diabetes trial is currently underway. For the first time, the patient was transplanted with insulin-secreting islet cells grown in a gene-edited lab to avoid the immune system. This treatment is called VCTX210 and is hopeful that diabetics will one day enjoy the production of recovered insulin without taking immunosuppressant medications.
The announcement was made by CRISPR Therapeutics, which developed innovative gene editing technology, and ViaCyte, a biotechnology company dedicated to finding functional treatments for diabetes using stem cell-derived pancreatic cells.
We were fortunate to speak with Dr. James Shapiro, a clinical researcher for a new trial. Dr. Shapiro is a giant in this field. As a surgeon in the late 1990s, he performed the world’s first islet cell transplant for patients with type 1 diabetes, a technique known as the “Edmonton Protocol.” He is currently the director of the Clinical Islets and Liver Transplant Program at the University of Alberta in Edmonton, Canada.
Islet cell transplantation has proven safe and effective, but remains partially rare due to a lack of organ donors. As a result, Dr. Shapiro says such transplants are basically limited to patients with disastrous needs. For example, patients with extreme glucose management challenges, recognition of hypoglycemia, or advanced kidney disease. (They are also almost completely unavailable in the US). However, by growing in the laboratory from former pocket stem cells, we developed an almost “infinite” supply of islet cells.
The company recently created a wave when its competitor, Apex, also devised a solution using stem cells and announced that the implanted cells had been successful in clinical trials. The news was widely welcomed as a breakthrough, but it was caught. The first patient of vertex requires anti-rejection drugs so that his own body does not attack new islet cells.
Dr. Shapiro told me that the ongoing islet cell transplantation therapy, which requires immunosuppression, is primarily “a patient who is truly impossible to control type 1 diabetes, and who is facing a dangerous low in blood glucose levels, and that doesn’t include 5%, perhaps 10% of the type 1 diabetes population.”
“Immunosuppressive drugs are a major barrier to why we don’t have to transplant large numbers of cells today.”
This is because immunosuppressive drugs can have serious side effects.
“Risks include increased risk of cancer, increased risk of life-threatening infections, and side effects on the kidneys. They may also be toxic to the functioning of transplanted cells and the ability to produce insulin.”
“Therefore, if transplants can be performed without drugs of rejection anti-anti-agents, if successful, would be a milestone advancement in cell therapy in this disease.”
Dr. Shapiro went on to explain that pancreatic cell transplantation can potentially be used in a vast number of patients with “any form of diabetes” if it effectively avoids the immune system.
“If we had no lifelong risk before us (from immunosuppressive therapy), we could open the gate and include everyone, not just adults, but children and patients with type 2 diabetes.
“If this is shown to be safe and if it is shown to be effective, that’s another big case, but if these two are achieved in the trials, I think we’ll consider using more cell therapy like this.”
Gene editing is not just the proposed method to hide islet cells transplanted from the immune system. ViaceTe features an alternative solution to the work, with a porous pouch that encapsulates new islet cells and allows glucose and insulin to filter through the barrier, but filters out larger immune cells. The pinnacle of their competitors is reportedly working on a similar solution, comparing them to “TeaBag.” And earlier this month we reported in a lab that began using nanocarriers to provide small but accurate doses of immunosuppressants.
However, Dr. Shapiro believes that precision gene editing using CRISPR, a Nobel Prize-winning technology, could ultimately prove to be a winning strategy.
“I think the ability to modify cell surface immune signaling, not recognize cells and not be destroyed by the alloimmune system, is a huge advancement for all areas of transplantation. I respect it.”
A new breakthrough trial began with the first patient in the world who received transplants of these gene-edited islet cells. The patient “permitted the surgery without missing the beat.” The surgery does not sound very invasive and requires only “small incisions in the abdominal wall.”
In the end, as many as 10 patients could undergo this first round of implantation. Dr. Shapiro could have been free for volunteers in the exam and for other patients who previously provided themselves for the Viacite exam.
“These are amazing people, and they have spontaneously moved forward not necessarily to help themselves, but to help humanity. They are looking for a better future for their full-scale diabetes. We are extremely grateful for the courage and vision that these patients must take part in such trials.”
Researchers at Viaseete thaw stem cells for expansion. Image provided by Viacyte, Inc.
You never know how much work you need before your treatment is ready for prime time. Dr. Shapiro hesitated to give me a timeline.
“Patients want to hear when it’s available, but we’re tired of hearing ‘5 more years of treatment’ so we won’t talk about it. We talk about the challenges before us. Having a crystal ball is good, but at the same time I think we work by facing challenges and pinning them.
“Maybe these initial gene editing will come a long way for us, but maybe they aren’t perfect. I don’t know that yet. Maybe we’ll need more editing and optimization.”
Finally, I asked him a big question: Will VCTX210 be considered a “treatment” for type 1 diabetes if everything goes according to the plan?
“We are always paying attention to the word ‘treatment’. I think this could be much better than insulin therapy. I think this could provide a potential biological solution to this biological disease.
“Therapy is emotional language. This could be a potential treatment for this disease. If you transplant an endless source of cells, don’t need anti-rejection drugs, don’t need insulin, don’t need insulin, I think we’re all looking at it and saying it.
“Conclusion: This is an incredibly exciting and important trial. It was the first human trial, the first patient, and now I’m going to race. For me, it was a great privilege to be part of this.
(TagstoTranslate)Insulin (T)Intensive management (T)Islet cell transplantation (T)Islet cell (T)Hypoglycemia (Hypoglycemia) (T)Stem cells (T)Biacite
