The Therapeutic Potential of Intrabodies in Neurologic Disorders

Abstract

Single-chain Fv and single-domain antibodies retain the binding specificity of full-length antibodies but they can be cloned, selected, engineered, and manipulated as genes. When expressed intracellularly in mammalian cells these intracellular antibodies, or intrabodies, have the potential to alter the folding, interactions, modifications, or subcellular localization of their targets. These reagents have previously been developed as therapeutics against cancer and HIV. Since misfolded and accumulated intracellular proteins characterize several major neurodegenerative disorders, including Huntington disease (HD) and Parkinson disease, these disorders are prime candidates for intrabody therapy. In this article we review the extension of intrabody technology to the nervous system. Studies of HD have been used to develop the approach and anti-synuclein strategies are in the early stages of development. Such neurodegenerative diseases are therefore poised for engineered antibody approaches, which can provide a pipeline of novel therapeutics and new drug discovery tools.