As an autoimmune disease, type-1 diabetes is caused by the body’s own immune system attacking the cells in the pancreas that produce insulin. This has led to attempts to “reboot” the immune system in patients, but has only been met with partial success.
Now researchers say they have found out why these earlier attempts may have failed and, more impressively, how it can be fixed – even reversing type-1 diabetes in mouse models.
They found that the faulty immune system in people with type-1 diabetes failed to make a specific protein called PD-L1, and that this molecule has a strong anti-inflammatory effect when it comes to the condition. By taking the blood stem cells and engineering them to produce PD-L1, they showed that it can cure the autoimmune reaction in human and mouse cells in the lab, and in some cases reverse it in living mice.
“Blood stem cells have immune-regulatory abilities, but it appears that in mice and humans with diabetes, these abilities are impaired,” explains lead author Paolo Fiorina, from Boston Children's Division of Nephrology, in a statement. “We found that in diabetes, blood stem cells are defective, promoting inflammation and possibly leading to the onset of disease.”
It was previously thought that if doctors could reset the immune system of patients with type-1 diabetes, it could cure them. This process involved taking blood stem cells from a patient and culturing them, before wiping out the immune system. The stem cells that were harvested are then reinfused into the bones of the patient and the immune system rebuilt.
But this latest work, published in Science Translational Medicine, suggests that the condition might be caused – at least in part – by these blood stem cells that lack the ability to produce this certain molecule. This may explain why resetting the immune system doesn’t always work, because the stem cells that are harvested and then reinfused still have this fault.
It also provides a possible way to treat the condition. The researchers took some stem cells and, using a modified virus, inserted the missing bit of DNA that codes for PD-L1 into the cells. These were then injected back into mice with type-1 diabetes. In most cases, the treatment held off the condition in the short term, and in about a third of the murine models, the condition was reversed for their entire lifespan.
The next move is to look at how long this reversal lasts for and why it was only maintained over the lifespan of one-third of the mice. They also need to uncover how often the treatment would need to be given if extended to humans.