Researchers at the University of Toledo have developed an experimental vaccine that shows promise in the prevention of rheumatoid arthritis, a painful autoimmune disease that currently cannot be cured.
The results, detailed in an article published in the journal Proceedings of the National Academy of Sciences, represent a major breakthrough in research into rheumatoid arthritis and autoimmune diseases in general.
One of the most common autoimmune diseases, rheumatoid arthritis, occurs when the body’s immune system attacks and breaks down healthy tissue -; especially the lining of the joints in the hands, wrists, ankles and knees.
Some estimates suggest that rheumatoid arthritis affects up to 1% of the world’s population.
Despite its high prevalence, there is no cure and we don’t know exactly what is causing it. This is true of almost all autoimmune diseases, which is what makes their treatment or prevention so difficult. If we can successfully get this vaccine into the clinic, it would be revolutionary. “
Dr. Ritu Chakravarti, Assistant Professor at UToledo College of Medicine and Life Sciences and lead author of the article
Chakravarti has been studying a protein called 14-3-3 zeta and its role in immune pathologies, including aortic aneurysms and interleukin-17- for years; a cytokine that has been linked to autoimmune diseases. Based on their previous work, the research group focused on the protein as a potential trigger for rheumatoid arthritis.
Instead, they found the opposite.
Instead of preventing rheumatoid arthritis, the researchers discovered that removing the protein through gene editing technology in animal models resulted in severe, early-onset arthritis.
Under the new theory that the 14-3-3 zeta protein protects against rheumatoid arthritis, the team developed a protein-based vaccine with purified 14-3-3 zeta protein grown in a bacterial cell.
They found that the vaccine was potent and immediate; but durable -; Response of the body’s innate immune system that provides protection from the disease.
“To our happy surprise, rheumatoid arthritis completely disappeared in animals given a vaccine,” said Chakravarti. “Sometimes there is no better way than chance. We happened to get a wrong result, but it turned out to be the best result. Such scientific discoveries are very important in this area.”
In addition to suppressing the development of arthritis, the vaccine also significantly improved bone quality -; a finding that suggests that there should be long-term benefits after vaccination.
Currently, rheumatoid arthritis is treated primarily with corticosteroids, broad-spectrum immunosuppressants, or newer, more targeted biologics that target a specific inflammatory process.
While these therapeutics can relieve pain and slow disease progression, they can also make patients more susceptible to infection and, in the case of biologics, they can be costly.
“We haven’t made really big discoveries about the treatment or prevention of rheumatoid arthritis in many years,” Chakravarti said. “Our approach is completely different. This is a vaccine-based strategy based on a novel target that we hope can treat or prevent rheumatoid arthritis. The potential here is huge.”
Researchers have filed a patent for their discovery and are looking for partners in the pharmaceutical industry to support safety and toxicity studies in hopes of conducting a preclinical study.
Kim, J., et al. (2021) 14-3-3ζ: A suppressor of inflammatory arthritis. Procedure of the National Academy of Sciences. doi.org/10.1073/pnas.2025257118.