Potential new treatment for rheumatoid arthritis
doi:10.1038/nindia.2015.4 Published online 14 January 2015
By fusing the molecules of an anti-inflammatory protein with those of a peptide, researchers have developed a drug-delivery system that slowly releases the anti-inflammatory protein1. As this anti-inflammatory protein protects bone joints against rheumatoid arthritis, these drug carriers are potentially useful for treating the condition.
The human body copes with rheumatoid arthritis by producing immune proteins such as interleukin-1 receptor antagonist (IL-1ra), which stop the activity of inflammation-inducing proteins. Animal studies had shown that synthetic IL-1ra can alleviate the symptoms of rheumatoid arthritis. In humans, protein-degrading enzymes easily destroy this synthetic protein, reducing its ability to combat rheumatoid arthritis.
To increase the therapeutic efficacy of synthetic IL-1ra, the researchers synthesized three IL-1ra-carrying variants — IL-1ra1, IL-1ra2 and IL-1ra3 — by fusing molecules of specific peptides with synthetic IL-1ra molecules. They then probed the anti-arthritic efficacies and drug-releasing properties of these three IL-1ra variants.
They noticed that the IL-1ra variants arranged the drug molecules (IL-1ra) in a stick-like fashion, so that the drug molecules formed clusters. In drug-release studies, the researchers found that IL-1ra1 and IL-1ra3 released the drug molecules in a sustained manner for a week.
To explore the therapeutic efficacy of IL-1ra1, they injected arthritic mice with a single dose of this drug. This drug reduced bone destruction in the mice by 80%. The IL-1ra1 treatment also lowered the levels of tissue-damaging enzymes, whose levels increase in rheumatoid arthritis. This alleviated arthritic symptoms in mice by 35%.
In addition, IL-1ra1 was resistant to attack by proteinase K, a protein-degrading enzyme usually found in a physiological environment. The researchers say that the finding that injection of a single dose of IL-1ra1 suppressed arthritis symptoms in mice indicates its therapeutic efficacy and its potential to replace multiple injections with a single one.
1. Pasi, S. et al. Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis. Biomaterials 42, 121-133 (2015)