To build in such durability, Betre turned to a class of proteins called elastin-like polypeptides (ELPs). Once ELPs in solution reach a certain threshold temperature, they assemble into protein aggregates. Study collaborator Ashutosh Chilkoti, a professor of biomedical engineering at the Pratt School, previously had investigated the use of ELPs that clump at temperatures higher than normal body temperature for treating cancers.
ELPs aren't recognized by the body's immune system as foreign substances, and thus they have some unique advantages for biomedical applications, according to the researchers. Also, ELPs can be joined directly to genes that control the production of various proteins in cells, with the combination forming "fusion proteins." As the proteins degrade, they yield simple amino acids, which are the building blocks of all proteins.
By experimenting with composition, molecular weight and concentration of various ELPs, Betre developed a protein for use in joints that would precipitate out of solution and clump at normal body temperature.
When he injected the sticky ELP into the knees of rats, the protein proved to have a 25-fold longer half-life in the joint than a similar soluble protein, Betre reported in the journal article. Half-life is the time required for half the quantity of the protein to be broken down and eliminated from the joint space.
"At 12 hours, the soluble protein was already at a concentration in the joint below 10 percent of the injected dose," Setton said.
In contrast, the sticky ELP took about two weeks to fall to the 10 percent level in the animals' joints -- a "really substantial increase," she said.
Moreover, rats injected with the clumping ELP contained lower blood levels of the protein, suggesting that a protein drug paired to the ELP might also have the benefit of fewer side effects, Shamji said. This would be important, he said, because IL1RA c