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June 26th, 2015

New Drug Promises Relief from Tinnitus, Epilepsy

New Drug Promises Relief from Tinnitus, Epilepsy

Published on June 24, 2015

Drug stops overactive electrical signals
Neurophysiologists at the University of Connecticut (UConn) have discovered a new drug that may prevent tinnitus and treat epilepsy by selectively affecting potassium channels in the brain.  According to an article in the June 10, 2015 edition of The Journal of Neuroscience, Anastasios V. Tzingounis, PhD, and colleagues say that both tinnitus and epilepsy are caused by overly excitable cells that flood the brain with an overload of signals that can lead to seizures (epilepsy) or phantom ringing in the ears (tinnitus).

The authors report that roughly 65 million people worldwide are affected by epilepsy. While exact statistics on tinnitus are not easy to determine, the American Tinnutus Association estimates that two million people in the US suffer from disabling tinnitus.

Anastasios V. Tzingounis, PhD, University of Connecticut
According to Tzingounis and co-authors, the existing drugs available to treat epilepsy don’t always work and can have serious side effects. One of the more effective drugs, retigabine, helps open KCNQ potassium channels, which serve as the “brakes” that shut down the signaling of overly excited nerves.  Retigabine, however, has terrible side effects and is usually only given to adults who don’t get relief from other epilepsy drugs.  The side effects of retigabine include sleepiness, dizziness, problems with hearing and urination, and a disturbing tendency to turn patients’ skin and eyes blue.

In 2013, Tzingounis began collaborating with Thanos Tzounopoulos, PhD, a tinnitus expert at the University of Pittsburgh, to create a new drug candidate.  The new drug, SF0034, was chemically identical to retigabine, but included an extra fluorine atom.  Originally developed by SciFluor, the company wanted to know whether the compound had promise for treating epilepsy and tinnitus.

Thanos Tzounopoulos, PhD, University of Pittsburgh
Tzingounis and Tzounopoulos thought the drug had the potential to be much better than retigabine in treating both conditions.  They first had to determine if SF0034 worked on KCNQ potassium channels the same way retigabine does, and if so, if it would be better or worse.
The co-authors explain in their article that KCNQ potassium channels are found in the initial segment of axons, long nerve fibers that reach out and almost touch other cells.  The gap between the axon and the other cell is called a synapse.  When the cell wants to signal to the axon, it floods the synapse with sodium ions to create an electrical potential.  When that electrical potential goes on too long, or gets overactive, the KCNQ potassium channel kicks in. The result is that it opens, potassium ions flood out, and the sodium-induced electrical potential shuts down.

In some types of epilepsy, the KCNQ potassium channels have trouble opening and shutting down runaway electrical potentials in the nerve synapse.  Retigabine helps them open. According to the authors, there are five different kinds of KCNQ potassium channels in the body, but only two are important in epilepsy and tinnitus: KCNQ2 and KCNQ3.  The problem with retigabine is that it acts on other KCNQ potassium channels as well.  That’s why it has so many unwanted side effects.

When testing SF0034 in neurons, the researchers found that it was more selective than retigabine.  It appeared to open only KCNQ2 and KCNQ3 potassium channels, and to not affect the KCNQ 4 or 5 potassium channels.  The research showed that SF0034 was more effective than retigabine at preventing seizures in animals, and it was also less toxic.

The results are promising, and SciFluor plans to start FDA trials with SF0034 to test its safety and efficacy in people.  Treating epilepsy is the primary goal, but treating or preventing tinnitus is a secondary goal.

Source: UConn; Medical News Today

- See more at: http://www.hearingreview.com/2015/06/new-drug-promises-relief-from-tinnitus-epilepsy/#sthash.CjhrDhjU.dpuf

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