New treatment for autoimmune disease

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A research team from University of Utah Health in Salt Lake City has begun to look into disabling only the particular sets of immune cells that cause trouble in autoimmune conditions, while preserving the integrity of healthy immune cells so they can continue to do their job. The new research conducted in mouse models focuses on programmed cell death protein (PD-1) cells. PD-1 is a type of protein on the surface of certain cells, and it plays a key role in regulating the immune response.

In a healthy immune system, the researchers explain, two types of specialized cells B and T lymphocytes express PD-1, and they feature a mechanism that checks immune cells’ activity to prevent them from attacking healthy cells. In people with autoimmune conditions, that mechanism becomes ineffective, and immune cells mistakenly turn against the body.

This new molecule has three main components: an anti-PD-1 antibody fragment, the Pseudomonas exotoxin, and a protein called albumin-binding domain. Each of these three components plays a specific role: The antibody fragment attaches to PD-1-expressing cells, the toxin then kills these cells, and finally, the albumin-binding domain allows the molecule to keep circulating through the body.

Once they had created this molecule, the scientists tested its effectiveness in two different mouse models: first, in one simulating type 1 diabetes and then in a model of multiple sclerosis. In the case of the rodents with a simulation of type 1 diabetes, the newly developed therapy delayed the onset of the condition. Usually, diabetes-like symptoms would set in at 19 weeks in mice, but those that had received the new treatment only began developing such symptoms at 29 weeks.

Then, when the researchers tested the new molecule in a mouse model of multiple sclerosis, they saw even more encouraging results: The treatment stopped paralysis progression in the six mice involved. Moreover, these rodents even regained the ability to walk.
The researchers continued to monitor these mice for 25 days following treatment and found that the therapy continued to keep paralysis at bay.

While the scientists are very enthusiastic about how promising this new approach appears to be, they nevertheless caution that the molecule they developed can so far only be applied to mice. “To make similar therapeutics for people, we would need to find the anti-human PD-1 antibody, like the anti-mouse PD-1 antibody,” explains Chen. Still, he expresses hope that this is an achievable goal that may improve the outcomes for people living with autoimmune conditions.