Antibody Stifles Pain And Itch

An antibody developed by a research team at Duke University Medical Center not only suppresses the agony of pain, it also quells the irritation of itch in laboratory mice (Cell 2014, DOI: 10.1016/j.cell.2014.03.064). The two-for-one treatment works its magic by binding to a voltage-gated ion channel, dubbed Na_v1.7, that scientists previously thought is responsible only for pain sensing.

One of a family of nine membrane-spanning ion channels, Na_v1.7 helps nerve cells transmit pain signals by opening its central pore and allowing sodium ions to rush through. Pharmaceutical firms that want to design more effective painkillers have taken interest in the channel, but finding small molecules to block it has proven difficult. Na_v1.7 is structurally similar to its eight kin, so small molecules that bind to the channel also bind other family members, causing side effects.

With this selectivity problem in mind, Duke team leaders Seok-Yong Lee and Ru-Rong Ji turned to antibodies. “Antibody-antigen interactions are much more selective than small-molecule-protein interactions,” Lee explains.

In cell studies, the researchers demonstrated that their antibody sticks almost exclusively to Na_v1.7.

After observing that the antibody suppressed chronic and inflammatory pain in mice, the team tested whether the treatment modulated any other sensations. Surprisingly, it also had an impact on itch. For instance, rodents injected with the itch-inducing agent chloroquine followed by the antibody scratched significantly less than those injected with only chloroquine.

This is the most important paper on Na_v1.7 in years, says Glenn F. King, a professor who studies painkillers at the University of Queensland, in Australia.

Stephen G. Waxman, a neurologist at the Yale School of Medicine and West Haven VA Medical Center, in Connecticut, finds the paper’s connection between itch and Na_v1.7 particularly interesting. He calls attention to a recent report of three patients with a genetic mutation in Na_v1.7 who suffer short, recurrent bouts of intense itching (Pain 2014, DOI: 10.1016/j.pain.2014.05.006).

Since the antibody study went online on May 22, Lee says a number of pharma firms have expressed interest in his team’s patented Na_v1.7 strategy. He hopes to partner with one of them to generate an antibody that binds the human version of the channel.