Primate with type 1 diabetes becomes insulin-independent after receiving gene-edited cells without immunosuppression

In a new research project, published in the journal Cell Stem Cell, researchers in California have demonstrated they can stabilise glucose levels in a monkey with type 1 diabetes without using immunosuppressants through a transplant of genetically edited cells.

The genetically edited cells

The researchers took stem cells, a type of cell that can transform into almost all other cell types, from rhesus monkeys and grew them into islets. Islets are the clusters of cells in the pancreas where the insulin-making beta cells are. The researchers then genetically edited the islets to become ‘hypoimmune’, which means they can hide from the immune system. The cells had to not only hide from the immune attack that causes type 1, but also the body’s natural immune response to cells that come from a different animal.

Transplanting the hypoimmune islet cells

The researchers treated a type of monkey called a crab-eating macaque that had type 1 diabetes in this study. They stabilised the monkey’s glucose levels with insulin injections before transplanting the hypoimmune islets into its legs without giving it any drugs to suppress the immune system. Then, over 12 days, the researchers gradually reduced the insulin they were giving the monkey down to nothing.

Insulin independence achieved

A week after the transplantation, the monkey’s c-peptide levels, a measure of insulin production, had returned to normal. The monkey experienced tightly controlled blood glucose levels with no hypers over the six-month study period. The monkey’s c-peptide levels remained stable showing full insulin independence, meaning the researchers didn’t need to give it any insulin. The monkey was also continuously healthy, with no physical or behavioral issues other than a small amount of weight gain. The monkey’s body didn’t show any signs of immune recognition of the transplant or any immune response, showing the cells had successfully evaded its immune system.

Removal of the islet cells

After six months, the researchers deactivated the transplanted islet cells by destroying them with a chemical treatment. After this, the monkey’s blood glucose levels began to fluctuate, and it needed insulin injections again. The researchers did this to prove that the tightly controlled blood glucose levels and insulin independence were entirely because of the transplanted islets.

How is JDRF involved?

The experiment was done by Sana Biotechnology, a company that JDRF invests in through the T1D Fund, a JDRF initiative to driving cures for type 1 diabetes by catalysing private investment.

Dr Sanjoy Dutta, JDRF Chief Scientific Officer, said: “JDRF is dedicated to harnessing the power of research, advocacy, and community engagement to advance life-changing breakthroughs for type 1 diabetes. The development of cell therapies that replace the loss of insulin-producing cells could one day offer cures for type 1 diabetes. A key area of focus for JDRF is to develop strategies to protect these cells after transplantation that remove the use of broad immunosuppression.”

Next step: a first-in-human study

The researchers now need to run a clinical proof-of-concept trial where they transplant the hypoimmune islets into one person with type 1 diabetes. This clinical trial will be the first time the treatment has been given to a human (known as first-in-human) and will take place later this year, according to Sana’s Head of Hypoimmune Platform. The purpose of this is to assess the safety of the treatment, how well the islet cells survive and avoid the immune system, and whether the person can produce their own insulin as a result.

Dr Sanjoy Dutta said: “As a supporter and investor in Sana through the JDRF T1D Fund, we look forward to seeing if the results described in this paper translate into people, as they would represent a meaningful advance in the treatment of type 1 diabetes.”