An international team has created antibody fragments, dubbed nanobodies, to address challenges posed by an ion channel important in inflammation. The nanobodies tamped down skin and kidney inflammation in mouse models, and could become a new strategy in combating inflammatory disease.
While the inflammation-triggering P2X7 ion channel has been identified as a drug target, previous approaches have had limited success because they are not specific enough and cause harmful side effects. To boost specificity, the scientists designed nanobodies, or antibody fragments, to inhibit P2X7 on immune cells. The nanobodies are a more specific treatment because their size enables them to more precisely attach to the “nooks and crannies” of cell surface molecules, according to a statement. The research, led by Welbeck Danquah of the Institute of Immunology, University Medical Center Hamburg-Eppendorf is published in Science Translational Medicine.
They injected mouse models of kidney inflammation and allergic contact dermatitis with the nanobody treatment, which reduced inflammation and alleviated symptoms. Additionally, nanobodies in human blood were shown to be 1,000 times better at blocking the release of inflammatory molecules, such as interleukin-1β, when compared to small-molecule drug candidates.
“Our results show that nanobody technology can generate potent, specific therapeutics against ion channels, confirm P2X7 as a therapeutic target for inflammatory disorders, and characterize a potent new drug candidate that targets P2X7,” the scientists said in the study.
Other approaches in inflammatory disease include leveraging the body’s molecular “brake” that curbs inflammation and harnessing a genetic mutation that protects the body from fibrosis resulting from Crohn’s disease.