Masonic Medical Research Institute
Masonic Medical Research Institute is a research organization founded by the Grand Lodge of New York. The institute studies experimental cardiology with an emphasis on cardiac arrhythmias, ischemic heart disease and sudden cardiac death.
Current research programs
- Cardiac Electrophysiology – This program uses experimental models to examine the root cause of cardiac arrhythmias and to develop treatments for heart disease.
- Molecular Genetics – Using genetic sequencing techniques, scientists at the MMRI are studying inherited cardiac arrhythmia syndromes, including sudden cardiac death syndromes such as the Long QT syndrome, Short QT syndrome, Brugada syndrome and Early Repolarization syndrome.
- Molecular Biology – Genes suspected of causing genetic mutations are cloned and the mutation is inserted into a heterologous expression system so that the functional effect of the mutation can be evaluated, to further determine whether the genetic variant is the true cause of the disease.
- Stem Cell Research – This program is focused on generating induced pluripotent stem cells to be used in testing the safety and efficacy of new drugs, and also for the creation of human models of heart disease to improve understanding of arrhythmic syndromes and to custom design treatments and cures.
- Organ and Tissue Bioengineering – This is a long-term program studying the use of a combination of pluripotent stem cells and decellularized donor hearts to created human hearts for transplantation without the problem of rejection.
Past scientific research results
In 1973 Institute researchers showed that oscillatory after potentials was the basis for arrhythmias associated with digitalis toxicity. Over the next several years later they explored modulated parasystole and reflection as mechanisms of cardiac arrhythmias.
In the 1980s research staff worked to clarify the differences between epicardium and endocardium, and found that the presence of an action potential notch in epicardium, but not endocardium, is responsible for inscription of the electrocardiographic J wave. They found differences in the response of epicardium and endocardium to a variety of drugs and neurotransmitters.
The MMRI developed a blood substitute which was patented in 1990.
In the 1990s MMRI researchers discovered the M cell, confirming that the heart is made of several different cell types. In 1998 they uncovered the cellular basis for the various waves that appear on an electrocardiogram including the J, T and U waves.
Between 1996 and 1998 MMRI published the first gene, SCN5A, to be linked to idiopathic ventricular fibrillation. The MMRI named this the Brugada syndrome in 1996, after Josep and Pedro Brugada, who first described this as a new clinical entity in 1992, and in 1999 proposed use of quinidine and isoproterenol for its treatment.
In 2000 the MMRI research team uncovered evidence linking Sudden Infant Death Syndrome to a congenital heart defect, the Long QT syndrome published in The New England Journal of Medicine. That year they also found experimental evidence, confirmed by later research, that some forms of early repolarization could result in the development of life-threatening arrhythmias.
During the next few years MMRI discovered several genes that when mutated give rise to the Long QT, Short QT, Brugada and Early Repolarization syndromes. They later demonstrated that, ranolazine, a drug approved for ischemic heart disease, was capable of suppressing both atrial and ventricular arrhythmias.
In 2007 MMRI researchers studied atrial-selective sodium channel block as a strategy to manage atrial fibrillation. They later demonstrated that the combination of ranolazine and dronedarone could prevent the development of atrial fibrillation, which led to Phase 2 clinical trials.
In 2010 MMRI described “J Wave Syndromes” a subset of inherited cardiac arrhythmia syndromes characterized by accentuated J waves, including the Brugada and Early Repolarization syndromes. Soon after, the research team identified Wenxin Keli, a herbal Chinese medicine, as an atrial selective sodium channel blocker capable of suppressing atrial fibrillation in experimental models. In 2012 they also identified Wenxin Keli and Milrinone as potential pharmacological therapies for the Brugada syndrome.
Education and training
The MMRI offers a Postdoctoral Fellowship Program as well as a Predoctoral Research Training Program which is administered in affiliation with SUNY Upstate Medical University at Syracuse, New York. Its ten-week Summer Fellowship Program, initiated in 1960, provides hands-on experience in research to students in the life sciences. MMRI also operates Mentoring Programs with BOCES, tours and shadowing programs to provide information to high school students about careers in science and research.Selected publications
- Moe GK, Rheinboldt WC, Abildskov JA. A computer model of atrial fibrillation. Am Heart J 1964;67:200-220.
- Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties in the deep subepicardium of the canine ventricle. The M cell. Circ Res 1991;68:1729-1741.
- Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol 1992;20:1391-1396.
- Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST segment elevation. Circulation 1999;100:1660-1666.
- Schwartz PJ, Priori SG, Dumaine R, Napolitano C, Antzelevitch C, Stramba-Badiale M, Richard T, Berti MR, Bloise R. A molecular link between the sudden infant death syndrome and the long-QT syndrome. N Engl J Med 2000;343:262-267.
- Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms. J Electrocardiol 2000;33:299-309.
- Burashnikov A, Di Diego JM, Zygmunt AC, Belardinelli L, Antzelevitch C. Atrium-selective sodium channel block as a strategy for suppression of atrial fibrillation: differences in sodium channel inactivation between atria and ventricles and the role of ranolazine. Circulation 2007;116:1449-1457.
- Burashnikov A, Sicouri S, Di Diego JM, Belardinelli L, Antzelevitch C. Synergistic effect of the combination of dronedarone and ranolazine to suppress atrial fibrillation. J Am Coll Cardiol 2010;56:1216-1224.
- Antzelevitch C, Yan GX. J wave syndromes. Heart Rhythm 2010;7:549-558.
- Burashnikov A, Petroski A, Hu D, Barajas-Martinez H, Antzelevitch C. Atrial-selective inhibition of sodium channel current by Wenxin Keli is effective in suppressing atrial fibrillation. Heart Rhythm 2012;9:125-131.
- Minoura Y, Panama BK, Nesterenko VV, Betzenhauser M, Barajas-Martinez H, Hu D, Di Diego JM, Antzelevitch C. Effect of Wenxin Keli and quinidine to suppress arrhythmogenesis in an experimental model of Brugada syndrome. Heart Rhythm. In press 2013.