Investigational vaccine shows great promise in preventing rheumatoid arthritis



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Researchers at the University of Toledo have developed an experimental vaccine that shows great promise in preventing 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 the study of 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 destroys healthy tissue; more particularly 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 are not quite sure what causes it. This is true for almost all autoimmune diseases, which makes their treatment or prevention so difficult. If we can get this vaccine into the clinic, that 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 for years a protein called 14-3-3 zeta and its role in immune pathologies, including aortic aneurysms and interleukin-17-; a cytokine associated with autoimmune diseases. Based on their previous work, the research group focused on protein as a potential trigger for rheumatoid arthritis.

Instead, they found the opposite.

Rather than preventing rheumatoid arthritis, the researchers found that removing the protein by gene-editing technology caused severe early-onset arthritis in animal models.

Working on a new theory that the 14-3-3 zeta protein protects against rheumatoid arthritis, the team developed a protein-based vaccine using the purified 14-3-3 zeta protein grown in a bacterial cell.

They found that the vaccine promoted a strong and immediate -; but durable -; response of the body’s innate immune system, providing protection against disease.

“To our surprise, rheumatoid arthritis completely disappeared in the animals that received a vaccine,” said Chakravarti. “Sometimes there is no better way than luck. We got a bad result, but it turned out to be the best result. This kind of scientific discovery is very important in this area.”

In addition to suppressing the development of arthritis, the vaccine also significantly improved the quality of bones -; a finding that suggests there should be long-term benefits after vaccination.

Currently, rheumatoid arthritis is treated primarily with corticosteroids, large-scale immunosuppressive drugs, or newer, more targeted biologics that target a specific inflammatory process.

While these treatments can relieve pain and slow disease progression, they can also make patients more susceptible to infections and, in the case of biologics, can be expensive.

“We haven’t made very big breakthroughs in treating or preventing rheumatoid arthritis in many years,” said Chakravarti. “Our approach is completely different. It is a vaccine strategy based on a new target which we hope will be able to treat or prevent rheumatoid arthritis. The potential here is enormous.”

The researchers have filed a patent on their discovery and are seeking pharmaceutical industry partners to support safety and toxicity studies in hopes of establishing a preclinical trial.

Source:

Journal reference:

Kim, J., et al. (2021) 14-3-3ζ: An inflammatory arthritis suppressor. Proceedings of the National Academy of Sciences. doi.org/10.1073/pnas.2025257118.

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