Nanobodies Show Unique Promise To Prevent Human Inflammation and Pain
In the ongoing research to control pain and inflammation, a special subgroup of antibodies called “nanobodies” have demonstrated this ability in a mammalian model for the first time. According to research published earlier this month on a study led by Friedrich Koch-Nolt, it also exposed nanobodies to human blood ex vivo and observed similar results. These tremendous findings may have profound medical repercussions for human patients.
Anobodies are single domain antibody fragments. Like complete antibodies, the antigen binding domain shows great specificity and affinity for its target molecule. In this case the target is the ligand-gated ion channel P2X7 found on the white blood cell.
When activated, the ion channel triggers a inflammation-inducing biochemical signaling cascade. If blocked from opening by nanobodies, the researchers postulated that inflammation could be halted in its tracks.
To test their predictions, mice models of allergic contact dermatitis and glomularnephritis – both inflammatory conditions – were infused with anti-P2X7 nanobodies. The researchers found that the mice treated with these special antibodies exhibited greater effective control of inflammation AND pain than cohorts treated with whole antibodies or anti-inflammatory medication.
In a further proof of concept experiment, the research team introduced anti-P2X7 nanobodies to human blood treated with endotoxins. Not only did the nanobodies prevent P2XD ion channels from activating the inflammatory cascade, they were 1000 times more potent than comparable medication treatments.
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These results, published in Science Translational Medicine, are promising as a future treatment for autoimmune diseases and chronic inflammation. When wayward immune cells wreak havoc on healthy tissue, they employ the same chemical messenger cascade used to disable pathogens. As such, switching off the P2X7 ion channel with nanobodies would fully curtail the errant inflammatory signal.
Nanobodies were first characterized by research in 2005 occurring naturally in llamas, camelids, and sharks. Although the human immune system does not produce single domain antibodies, humanized nanobodies can be engineered in vitro using cellular techniques such as polymerase chain reaction.
Sources: Science Translational Medicine, livescience