Atrial fibrillation is the most common cardiac arrhythmia, yet its causes are not fully known and present treatment modalities are only partly effective. Genetic studies of three generations of a Jewish family of Iranian descent conducted at BGU have identified a previously unknown mechanism for the disease: the mostly night-time atrial fibrillation was shown to be caused by a mutation in a gene (KCND2), encoding a crucial component of a potassium ion channel (Kv4.2) in the heart.
In light of its specificity to the cardiac atria and its night-time expression, this channel is an optimal drug target for novel treatment modalities of atrial fibrillation. The research team, within the National Institute for Biotechnology in the Negev (NIBN) and the Faculty of Health Sciences on BGU's campus, is in the preliminary stages of developing an anti-arrhythmia medication, based on the findings.
Combining genetic studies with frog oocyte and mutant mouse analyses, the research group demonstrated that the mutation increases conductivity of the channel, thus greatly enhancing predilection to atrial fibrillation. This ion channel is unique in that it is expressed specifically in the cardiac atria, and has circadian rhythm: It is expressed at significantly higher levels during the night-time, explaining why its mutation causes atrial fibrillation specifically at night.
The clinical studies were conducted by Prof. Amos Katz, cardiologist and Dean of the Faculty of Health Sciences at BGU, and Dr. Menahem Sasson, the family's physician. The molecular and genetic studies were conducted by Max Drabkin, an MD-PhD student from the Joyce and Irving Goldman Medical School, mentored by Prof. Ohad Birk, head of Soroka University Medical Center's Genetics Institute and its Naomi Fisher-Bartnoff Genetic Counseling Unit, as well as the National Center for Orphan Diseases and the Morris Kahn Laboratory of Human Genetics at BGU.
Other researchers include Prof. Noam Zilberberg and Prof. Yoram Etzion, as well as several graduate students of the Birk lab, all at BGU. Max Drabkin was awarded the highly competitive Foulkes Foundation MD-PhD scholarship through the Israel National Academy of Sciences for this study.
Their findings were published in the prestigious cardiology journal: Circulation: Genomic and Precision Medicine.
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