Fusion Protein Relieves Nine Mice of Collagen-Induced RA

August 12, 2014

An IL4 fusion protein has completely resolved rheumatoid arthritis in a mouse study using a standard collagen-induced model of the disease.

Hemmerle T, Doll F, and Neri D. Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis. Proceedings of the National Academy of Sciences (2014). Online August 4, 2014, doi/10.1073/pnas.1402783111

In case someone asksabout the arthritis "cure" they read about in the newspaper: Swiss researchers report that a fusion protein resolved disease in nine mice with a standard collagen-induced model of rheumatoid arthritis (RA).

One of the authors (Neri) has co-founded a company to produce the antibody. Human trials are expected within a year.

The fusion protein is a combination of F8 antibody and interleukin-4 (IL4). The antibody binds to fibronectin, a marker of angiogenesis, which is strongly overexpressed at sites of arthritis. This iinterleukin stimulates the production of T helper type 2 cells. 

IL4 has shown some effectiveness in preclinical studies of RA, but its potency was low. The idea behind this study was to improve its effectiveness by fusing it to F8, which should deliver it to the location of RA activity.

Neri is also investigating an F8-interleukin-10 fusion protein, which had promising effects in a phase I trial.

This was a controlled study with six treatment groups of 7-8 mice each, including controls injected wtih an inert vehicle and IL4 or dexamethasone alone.

Nine mice with collagen-induced RA were injected with the F8-IL4 fusion protein and dexamethasone. In all of them, all detectable signs of arthritis disappeared.  The treatment also reduced levels of cytokines, particularly several inflammatory interleukins and tumor necrosis factor.

The authors say that this is the first report of durable and complete regressions in mice with established RA.