Kv1.3 was a hot topic at this meeting, and I saw some great posters and talks on Monday suggesting that this channel is a potential target for the treatment of autoimmune and inflammatory diseases. Here’s a rundown of the different approaches I being used by researchers at BPS18 and some of the purported health implications of specific Kv1.3 pharmacology.

A group of scientists working together across industry (TetraGenetics, Inc., Crystal Bioscience, and argenx) and academia (Cornell and UC Davis) are developing monoclonal antibodies against Kv1.3 in chickens and llamas, and they appear to have one candidate that specifically reduces current from human Kv1.3 expressed in HEK293 cells. The mAb has an EC50 of a few nM and doesn’t act on other shaker type channels, hERG, or voltage-gated sodium channels. Unlike most ion channel antibodies, these are raised against an entire Kv1.3 subunit (purified from Tetrahymena thermofila), which is likely how they’ve managed to produce an antibody with an effect on channel function.

A graduate student in Debra Fadool’s lab at Florida State Univeristy has been modifying fluorescent nanoparticles with Margotoxin and delivering them to the olfactory bulb to inhibit Kv1.3 expressed in mitral cells. MgTx is a commonly used agent for blocking Kv1.3 for research purposes, but targeted delivery in vivo can be difficult. Interestingly, when cannulated into the mouse olfactory bulb, MgTx-nanoparticles appear to help maintain normal bodyweight in rodents – perhaps highlighting a connection of Kv1.3 function and the regulation of metabolism.

Heike Wulff from UC Davis gave a talk and showed that Kv1.3 expression in microglia is upregulated after ischemic stroke, suggesting an inflammatory response to this stimulus in the brain. Interestingly, her well-characterized Kv1.3 inhibitor (PAP-1) minimizes this inflammatory response after insult and improves performance on rodent neurological function assays.

And lastly, although he didn’t specifically mention Kv1.3 as a current target, Damien Bells from Iontas, Inc. gave us a glimpse into their most recent KnotBody™ technology, which they think is the future of ion channel pharmacology. The idea is to combine tissue specific antibodies with ion channel specific knottin motifs to create highly effective blockers of ion channels that work in vivo. These structures are exciting because they harness the power nature’s own mechanisms for modulating channel function, but the modular structure of KnotBodies allows for extensive optimization on the channel and tissue level.

If you’re interested in mechanisms underlying inflammation and autoimmune disease, you may want to keep your eye on these scientists and their work with Kv1.3!

--Emily E. Maverick