Genetic Diagnosis for QT Syndrome-Related Adverse Drug Reactions

Reference #: 1999-026

OTC Contact: Tracy Bruehs, M.S., J.D., Associate Director for Licensing and Contracts, (202) 687-7629 (Directory Information | Send a Message)

Description

Adverse drug interactions are increasing among patients (e.g., Phen-Fen and Seldane). Over 40 drugs (marketed and in development) have been shown to prolong the cardiac QT interval, as seen on an ECG, via blocking cardiac repolarization channels. Under certain circumstances, these drugs can cause some people to experience a potentially lethal cardiac arrhythmia referred to a Torsades de Pointes. Until now, no single genetic test has been able to identify persons at risk of this adverse event. Thus, this invention is a novel and very useful genetic diagnostic tool that can be used to identify which patients would be susceptible to an adverse drug reaction having an effect of prolonged cardiac repolarization, prior to administration of a drug.

Applications

The diagnostic could be used by physicians to screen patients for their susceptibility to suffer a potentially lethal adverse drug reaction prior to prescribing drugs that prolong the QT interval.
The diagnostic could be used by drug companies to safely exclude “at risk” subjects or patients from clinical trials, thereby, reducing or avoiding malpractice suits.
Enhances FDA approval process by reducing patient risk pool.

Advantages

Stage of Development

The diagnostic tool is a screen comprised of a nucleic acid or DNA array or chip that is encoded as a genetic probe to identify certain protein sequences, mutations, and/or genetic polymorphisms within a subject’s biological sample, specifically identifying presence of mutations along the QT associated genes (LQT 1,2,3,5,6 genes), altered sensitivity genes (MiRP1 or related genes), and/or increased exposure genes (cytochrome P450 genes and MDR genes).

There are approximately 50 or more drugs on the market and in development that prolong the QT interval on the ECG, including tricyclic antidepressants, antiarrhythmics, non-sedative antihistamine toxicity, antimalarials, antipsychotics, and cisapride. In certain situations these drugs can cause in some people to develop a lethal cardiac arrhythmia, torsades de pointes. Torsades is a form of ventricular tachycardia that can most often be due to medication. Torsades can be influenced by many factors, i.e., genetic determinants of the ion channels, separate genes that control the adrenergic tone and separate genes that control sex hormones. This invention combines the genetic information for all of these genes into a DNA array (chip) that can predict individuals’ chances of being harmed by drugs that prolong the cardiac repolarization prior to administration of these drugs. This application may also apply to drugs currently in development or early stage, and would serve as a very useful personalized medical tool.

Relevant Publications

N/A

Patent Status

Issued U.S. Patent No.: 7,179,597, issued 2/20/07 EPC Application No.: 01926956.2 issued.