Date: Jun 04, 2015 Source: Business Wire (
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SEATTLE--(BUSINESS WIRE)--In a study published this week in the European Journal of Heart Failure, University of Washington researchers reveal that cardiac-specific gene therapy using BB-R12, a novel biological therapy being developed by UW startup BEAT BioTherapeutics Corporation (BEATBio), may reverse the cardiac dysfunction that causes heart failure. The study, conducted in a pig heart failure model by a team of scientists from BEATBio and the UW departments of medicine and bioengineering, showed that a single treatment with BB-R12 leads to persistent improvement in multiple measures of heart failure severity.
"The results of this study move us from rodent models forward, toward clinical testing based on BB- R12's ability to reverse heart failure in a predictive pre-clinical model," said BEATBio Co-founder Michael Regnier, UW professor and vice chair of bioengineering, and head of the Heart and Muscle Mechanics Laboratory.
Results from earlier studies have shown that increasing the activity of the protein ribonucleotide reductase (RNR) in the heart leads to improved cardiac performance via synthesis of deoxy-ATP (dATP), a naturally occurring molecule that powers muscle contraction. UW researchers discovered an important pathway that nature uses to regulate heart contractility: the same pathway that heart cells use to make the building blocks for DNA during embryonic growth also makes dATP to supercharge contraction whenever the adult heart becomes mechanically stressed. These findings suggest that treatments that elevate dATP levels in heart cells may prove to be an effective treatment for heart failure. The current study extends these observations to a human-relevant, large animal model of heart failure using BB-R12, a human gene therapy vector construct, and suggests that BB-R12 can rescue heart function following a heart attack.
Regnier said a related paper published in the Journal of Molecular and Cellular Cardiology showed that BEATBio's therapeutic approach improves cardiac function in end-stage human heart failure. That study demonstrated that dATP activates myosin -- the protein responsible for heart contractions -- in the cells, increasing the speed and force of contraction in cardiac muscle taken from human patients with end-stage heart failure.
BB-R12 is the first heart failure gene therapy with a mechanism of action that is independent of calcium regulation. Gene therapy using BB-R12 increases cardiac function by turning a small number of cardiac muscle cells into cellular factories that generate dATP. dATP increases the performance of both the transduced cell and adjacent cardiac muscle cells because dATP can diffuse from cell to cell through normal structures called gap junctions.
"The collaboration between BEATBio and UW has been very fruitful," said BEATBio CEO Michael Kranda. "As a company, we are now building upon years of research conducted at UW to advance BB-R12 towards clinical trials to treat heart failure. Heart failure has reached epidemic proportions in the U.S. and globally due to the number of people experiencing mortality, morbidity, and impaired quality-of- life. If successfully developed, BB-R12 will make a big difference for many patients."
About BEATBio: BEATBio is a Seattle, Wash. based biotechnology company focused on the development of BB-R12, a novel biological treatment for heart failure. BB-R12 is a gene therapy based on increasing myocardial dATP to improve cardiac muscle contraction and is based on years of research in Dr. Regnier's lab. BEATBio's founders, from the University of Washington, are recognized experts in cardiovascular biology, muscle physiology and bioengineering and have received nearly $50MM of NIH funding. BEATBio holds exclusive, worldwide rights to the BB-R12 technology and has used a recently raised $4 million seed financing to successfully complete the initial stages of pre-clinical development and manufacturing scale-up. BEATBio has assembled a strong team of experts that has allowed rapid achievement of significant development milestones in 2013-2014. The company is now raising a Series A financing to complete IND-enabling studies and complete Phase I human trials.
