UMN-123 – Permanently charged PUFAs to treat cardiac arrhythmias

Problem: Cardiac arrhythmias (“arrhythmias”)—also known as irregular heart beat—are one of the most common causes of death in Western countries today. Interference with cardiac electrical impulses causes the heart to beat too fast, too slowly, or erratically. To ensure a constant, regular heartbeat, the heart relies on a series of sodium, calcium, and potassium channels. Disruptions to activity in the IKS channel—one of the major repolarizing cardiac potassium channels—may cause fatal conditions such as: (1) loss-of-function mutations (Long QT Syndrome) that lead to Romano-Ward syndrome, Jervell and Lange-Nielsen syndrome, Short QT Syndrome, fainting, seizures, ventricular arrhythmias, ventricular fibrillation, and sudden cardiac death; (2) gain-of-function mutations (Short QT Syndrome) that lead to atrial fibrillation and blood clot formation. If severe or long lasting, arrhythmias may lead to ineffective blood circulation—which in turn, can cause cessation or damage to the lungs, brain, and all other organs. Technology: Effective treatment of an irregular heartbeat requires medicine to cause disruption, and therefore modulation, to IKS channel activity. The invention does this by placing the IKS channel in contact with compounds that activate or inhibit the channel as needed. In order to modulate the IKS channel, the channel is contacted with polyunsaturated fatty acids (PUFAs), which will by their negative or positive charge affect the channel and disrupt the irregular activity of the channel. This treatment could restore regular cardiac function of even the most severe loss of function cardiac mutations that result in fainting, seizure, or sudden cardiac death. For example, a negatively charged PUFA can decrease the length of the ventricular action potential to reverse the effect of Long QT mutations. Conditions resulting from an increase in the length of ventricular action potential include, e.g., Long QT Syndrome, fainting, seizure, or sudden cardiac death. Peter Gutenberg pxg372@miami.edu 305-243-4604