New option for treating type 1 diabetes shows promising preclinical results

Receive a type 1 diagnosis Diabetes today means a lifetime of insulin injections – at the moment we don’t have a single simple solution at hand.

To date, every breakthrough promising a cure for diabetes encountered significant obstacles, making it unviable for the vast majority of people. Now researchers in the United States have improved a type of transplant-based treatment, potentially giving hope of the 9 million people in the world with this state.

“The immune system is a tightly controlled defense mechanism that ensures the well-being of individuals in an environment full of infections,” explains one of the researchersUniversity of Missouri immunologist Haval Shirwan.

“Type 1 diabetes develops when the immune system mistakenly identifies insulin-producing cells in the pancreas as infections and destroys them.”

These insulin-producing cells are grouped together in clusters called pancreatic islets, which eventually get destroyed by faulty immune cells in the body.

Useful treatments include an islet cell transplant, or a transplant of a whole pancreas, to provide more islets for insulin production. However, these are not without risks; people who receive a transplant must also take immunosuppressive drugs for the duration of the transplant, to make sure the rogue immune cells don’t also destroy the new tissue.

“Islet transplant recipients must be immunocompromised for the rest of their lives with agents that not only are toxic to the recipient and the β-cells of the graft, but can also induce peripheral insulin resistance,” writes the team in their new diary.

“Thus, the development of tolerogenic diets that avoid the need for immunosuppression will facilitate the widespread application of islet transplantation as a treatment for type 1 diabetes.”

In a preclinical study using cynomolgus monkeys (also known as the crab-eating macaque) the team had incredible success transplanting islets combined with a microgel containing FasL – a protein involved in cell death – on its surface.

“A type of apoptosis occurs when a molecule called FasL interacts with another molecule called Fas on rogue immune cells, and it causes them to die,” says University of Missouri immunologist Esma Yolcu.

“Therefore, our team pioneered a technology that enabled the production of a new form of FasL and its presentation on transplanted pancreatic islet cells or microgels to avoid being rejected by rogue cells. .

“After transplantation of insulin-producing pancreatic islet cells, the rogue cells mobilize towards the transplant to be destroyed but are eliminated by FasL, engaging Fas on their surface.”

This is not the only change from a traditional transplant. Instead of transplanting the cells into the liver (the typical clinical route), the researchers formed a small pocket in the omentum, a large, flat layer of fatty tissue just below the stomach.

“Unlike the liver, the omentum is a non-vital organ, allowing its removal in the event of undesirable complications,” he added. says lead author Ji Lei, an immunologist at Massachusetts General Hospital.

“Thus, the omentum is a safer place for diabetes treatment transplants and may be particularly well suited for stem cell-derived beta cells and bio-engineered cells.”

Four of the monkeys received the FasL microgels, while three controls received microgels without FasL. The researchers then gave the monkeys a single anti-rejection drug called rapamycin for three months after the transplant surgery.

After that, the drugs were stopped and the monkeys that had received the FasL treatment all maintained their glycemic control for the entire study period – up to 188 days after surgery.

Unfortunately, the experiment had to be cut short due to COVID-19[feminine]but compared to controls, who maintained glycemic control for only one month on average, this is an excellent result.

“Our strategy to create a local immune-privileged environment enabled islets to survive without long-term immunosuppression and achieved robust glycemic control in all diabetic non-human primates over a study period. six months, Lei said.

“We believe that our approach enables the grafts to survive and control diabetes for well over six months without anti-rejection drugs, as surgical removal of the grafted tissue at the end of the study resulted in the rapid return of all animals to a diabetic state.”

Although planning for a human clinical trial is beginning, there is still a long way to go before it is something a type 1 diabetic patient can actually expect to receive.

Also, it’s important to note that monkeys – although very similar – are not humans. For example, the researchers point out that the omentum in monkeys is a much thinner membrane than in humans, so the results could be different.

We will need more research to know for sure.

Nonetheless, this is an impressive result, and team members have filed a patient file and created a new company to bring their findings to clinical tests.

The research has been published in Scientists progress.

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