Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death.

ABSTRACT: Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion cha

SUBMITTER: Qiang M 

PROVIDER: S-EPMC6094137 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature