2020-008 – P2X4 scFv Antibodies as a Non-opioid Therapeutic for Pain Management

Background Less than thirty percent of Americans who suffer from chronic pain are effectively treated by current therapies. Opioids as therapeutic agents, in particular, are significantly limited by their addictive and detrimental side effects, including sedation, respiratory depression, constipation, and tolerance. In order to effectively treat chronic pain, without the risk of damaging side effects, non-opioid alternatives must be identified. Antibody therapy is a relatively new technique that exploits the high selectivity of conditioned monoclonal antibodies (mAbs), resulting in the specific targeting of a cell or protein type. These antibody-based therapies have even been applied in Alzheimer’s and Parkinson’s treatment. Despite the success of mAbs, the development process is laborious and succumbs to difficulties generating antibodies against self-antigens. Thus, there has been a switch toin vitrodisplay techniques, such as phage and ribosome display. Single-chain variable fragments (scFvs), a type of antibody produced via ribosomal display, have demonstrated stronger tissue and brain permeability, compared to antibodies developed via phage display. The increased brain permeability allows for specific targeting of locations, within the neural complex, responsible for chronic pain. The scFvs can be easily modified with anin vivohalf-life for short-term diagnostic or long-term biotherapeutic applications for both the nervous and immune systems. Further understanding of scFvs and their advantages will enhance their potential as chronic pain therapeutics. Technology Description Researchers from the University of New Mexico and Loyola University Chicago have found an innovative application for scFv antibodies, in the treatment of chronic neuropathic pain. The P2X4 purinergic channels are identified as primary channels increased by pain. They are a means through which pro-inflammatory cytokines and other active neuronal substances are released following injury that amplify pain. The P2X4 purinergic channels are increased by pain and are a means through which pro-inflammatory cytokines and other active neuronal substances are released that amplify pain following injury. Data indicate that a single dose of P2X4 scFv effectively returns the mechanical threshold pain measure to naïve baseline for many weeks in a nerve injury chronic pain animal model. As a beneficial side effect, the P2X4 scFv reduces anxiety and depression. The scFvs offer extreme specificity, high affinity, brain penetrance, superior stability and solubility, and large-scale production ease. These advantages, along with, the ease of large-scale production due to the ribosomal display, provide evidence that scFvs can be utilized as a viable treatment method for chronic neuropathic pain. Gregg Banninger GBanninger@innovations.unm.edu 505-272-7908

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