Promising Pre-Clinical Results Show Up For Type 1 Diabetes Treatment

Promising Pre-Clinical Results Show Up For Type 1 Diabetes Treatment ...

As of today, being diagnosed with type 1 diabetes means a lifetime of insulin injections, but we do not have a simple one-time fix.

Despite their significant obstacles, each breakthrough in achieving a diabetes treatment has made it possible for the vast majority of people. Researchers in the United States have improved on one type of transplant-based treatment, posing a threat to the world''s 9 million people.

"The immune system is a tightly controlled defense mechanism that assures the well-being of individuals in an environment full of infections," says one of the researchers, an immunologist from the University of Missouri.

"Type 1 diabetes develops when the immune system misidentifies the insulin-producing cells in the pancreas as infections and destroys them."

These insulin-producing cells are grouped into pancreatic islets, which are eventually destroyed by the malfunctioning immune systems of the body.

To provide more islets for insulin production, an islet cell transplant or a pancreas transplant aren''t without problems. Nevertheless, transplants do not only involve risks, but individuals who receive immunosuppressive medications can also prolong the life of the transplant, ensuring that the rogue immune cells do not damage the new tissue.

"Islet graft recipients must be immunosuppressed for the remainder of their lives with agents that are non-toxic to the recipient and graft cells, but also may inhibit peripheral insulin resistance," the team''s new study says.

"Thus, the development of tolerogenic medications that avoid immunosuppression will help with the broad application of islet transplantation as a cure for type 1 diabetes."

In a preclinical experiment using cynomolgus monkeys (also known as the crab-eating macaque), the team achieved incredible success by 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 the University of Missouri immunologist.

"Our team" patented a technology that enabled the production of a new form of FasL, including its presentation on transplanted pancreatic islet cells and microgels, to prevent being rejected by rogue cells.

"Rogue cells mobilize to the graft for destruction, but FasL removes them, putting Fas on their surface."

This is not the only difference from a traditional transplant. Instead of transplanting the cells to the liver (the typical clinical route), the researchers formed a small pouch in the omentum, forming a large flat layer of fat tissue just below the stomach.

"Unlike the liver, the omentum is a non-vital organ, which permits its removal if undesired complications arise," says the author, an immunologist at the Massachusetts General Hospital.

"Thus, the omentum is a safer location for diabetes transplants and might be particularly suitable for stem-cell-derived beta cells and bio-engineered cells."

Four of the monkeys received the FasL microgels, while three of the monkeys received microgels without FasL. Afterwards, the monkeys received only one anti-rejection medication called rapamycin, which was then given to the monkeys for three months after the transplant.

After that, the drugs were stopped, and monkeys that received the FasL therapy maintained their glycemic control for the whole study period until 188 days post-surgery.

Due to COVID-19, the experiment arose, but compared to controls, which maintained glycaemic control for a month in average, this is a wonderful result.

"Our goal to create a local immune-privileged environment allowed islets to survive without long-term immunosuppression and achieved robust blood glucose control in all diabetic nonhuman primates during a six-month study period," says Lei.

"We believe that our approach allows transplants to live and manage diabetes for much longer than six months without anti-rejection medications, because surgical removal of the transplanted tissue at the conclusion of the study resulted in all animals returning promptly to a diabetic state."

While planning for a human clinical trial is beginning, there is still a long way to go before it''s something a type 1 diabetes patient might actually expect.

Despite their appearance, monkeys are not humans. For example, the researchers find that the omentum in monkeys is a much thinner membrane than in humans, thus the results may be different.

More research will be required to be done on the go.

Despite this, this is a fantastic outcome, and members of the team have filed a patient and started a new business to bring their findings to clinical trials.

Science Advances has released the findings.

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