An experimental protein-based vaccine against rheumatoid arthritis has shown huge promise in early animal models, according to new research from the University of Toledo. As an excruciatingly painful autoimmune disorder that affects around 1.5 million Americans currently, rheumatoid arthritis has no known cure and a vaccine would be a huge step in allowing millions of people to move once more.
“In spite of its high prevalence, there is no cure and we don’t entirely know what brings it on. This is true of nearly all autoimmune diseases, which makes treating or preventing them so difficult,” said Dr Ritu Chakravarti, an assistant professor in the UToledo College of Medicine and Life Sciences and lead author on the paper, in a statement. “If we can successfully get this vaccine into the clinic, it would be revolutionary.”
The research is outlined in PNAS.
Rheumatoid arthritis is an autoimmune disorder in which immune cells attack the lining of joints, degrading them progressively over time. There is no cure for rheumatoid arthritis, but early diagnosis can help alleviate symptoms to a liveable degree through the use of disease-modifying anti-rheumatic drugs (DMARDs), which block the effects of chemicals released when the immune system attacks the joints.
In the pursuit of a more substantial and preventative treatment, Chakravarti and colleagues identified a protein called 14-3-3 zeta. 14-3-3 zeta is an autoantigen (a protein recognized by our own immune systems) that is thought to play a role in inflammatory arthritis, and the researchers set out with the hypothesis that it may trigger the condition. Surprisingly, they found the exact opposite.
Using gene editing, the team took rats and knocked out 14-3-3 zeta, preventing its production, in the expectation that the rats may have reduced inflammatory arthritis. Instead, the rats developed severe early-onset arthritis, with the disease resulting in bone loss, immune cell infiltration, and destruction of joints. In the wake of this realization, the researchers tried to supplement the rats with more 14-3-3 zeta to try and stop disease progression, but it had no effect.
However, when they supplemented different rats with a vaccine packed full of 14-3-3 zeta, prior to them developing the condition, it resulted in suppression of arthritis onset in all rat models. The researchers now believe this protein may have an immunosuppressive effect, preventing inflammatory immune markers from attacking the body’s own cells while also preserving bone quality.
“Much to our happy surprise, the rheumatoid arthritis totally disappeared in animals that received a vaccine,” Chakravarti said.
“Sometimes there is no better way than serendipity. We happened to hit a wrong result, but it turned out to be the best result. Those kinds of scientific discoveries are very important in this field.”
This mechanism was previously unrecognized in rheumatoid arthritis research and may have huge implications if it translates to humans. As with all animal studies, there is now a long road to judge the safety and efficacy of such a vaccine in humans, but the research could be one of the largest breakthroughs in helping those with the condition in a long time. The team are now seeking a patent and looking for pharmaceutical partners to aid them in establishing a preclinical trial.
