Recent research explores a promising new pathway in the treatment of autoimmune conditions.
Current treatments for autoimmune conditions rely on neutralizing the immune cells that mistakenly target and attack the body’s own healthy tissue.
However, a major downside of existing therapies is that they end up inactivating not just the specific immune cells causing the damage, but also other immune cells that are functioning normally.
This leaves the body exposed to all kinds of other diseases and infections.
Now, 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.
The study’s findings, which were published yesterday in the journal Nature Biomedical Engineering, suggest that the new strategy may be a viable, more constructive approach to tackling autoimmune conditions.
“We are really taking treatment for autoimmune disease in a new direction. This is the first time anyone has looked at the [PD-1] cells as a target to develop therapeutics for autoimmune disease.”
Study author Mingnan Chen, Ph.D.
3 key components working in unison
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.
The first author of the current study, Peng Zhao, Ph.D., notes that the team “wanted to target PD-1-expressing cells” with the aim to “avoid long-term immune deficiency caused by common treatments for autoimmune disease.”
The researchers thus set to work to design a protein molecule that would have the effect of depleting the immune system’s store of PD-1-expressing cells.
This new molecule, the team explains, 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.
Novel approach ‘could make a huge impact’
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.
“If we can generate the human version of therapeutics, I think we could make a huge impact in treating autoimmune disease,” Chen says.