Biologic Pacemaker
Patent Number: WO2016141073A1
Executive Summary:
General Description:
The heartbeat originates in the sinoatrial node (SAN), a small structure located in the right atrium. The SAN contains specialized cardiomyocytes, the pacemaker cells, which spontaneously depolarize via mechanisms regulated by distinct ion channel and calcium handling protein expression within the node. The anatomic and molecular architecture of the SAN ensures electrical source-sink matching, preventing the node from becoming hyperpolarized and quiescent by the surrounding atrial cardiomyocytes, as well as allowing conduction of action potentials from the SAN to nearby atrial myocardium. The present invention is related to treating diseases of the cardiac conduction system using compositions and methods for converting cardiac tissue into pacemaker-like cells, and methods for treating sinus node dysfunction.
Future Directions:
Strengths:
Weaknesses:
Patent Status:
Publications:
Inventor Bio: Stacey Rentschler
https://cardiovascularresearch.wustl.edu/labs/stacey-l-rentschler-md-phd/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: US and PCT Granted
- Patent Link: https://patents.google.com/patent/WO2016141073A1/
- Research Institute: Washington University
- Disease Focus: Cardiovascular Disease
- Basis of Invention: Compositions and methods for converting cardiac tissue into pacemaker-like cells, and methods for treating sinus node dysfunction
- How it works: Infecting a cardiomyocyte with a composition comprising an adenovirus encoding a transcription factor, converting cardiac tissue to an induced-sinoatrial node (iSAN) for treating sinus node dysfunction (SND)
- Lead Challenge Inventor: Stacey Rentschler
- Inventors: Stacey Rentschler, David Curiel, Igor Efimov
- Development Stage: Human testing ex vivo
- Novelty:
- Solution longevity, no needs for update device surgery (Pediatric Population)
- Matching of heart rate with exercise intensity (sensitive to autonomic input)
- Appropriately sized to the patient
- Clinical Applications:
- Regenerative medicine
- Sinus node dysfunction, especially for pediatric population
General Description:
The heartbeat originates in the sinoatrial node (SAN), a small structure located in the right atrium. The SAN contains specialized cardiomyocytes, the pacemaker cells, which spontaneously depolarize via mechanisms regulated by distinct ion channel and calcium handling protein expression within the node. The anatomic and molecular architecture of the SAN ensures electrical source-sink matching, preventing the node from becoming hyperpolarized and quiescent by the surrounding atrial cardiomyocytes, as well as allowing conduction of action potentials from the SAN to nearby atrial myocardium. The present invention is related to treating diseases of the cardiac conduction system using compositions and methods for converting cardiac tissue into pacemaker-like cells, and methods for treating sinus node dysfunction.
Future Directions:
- In vivo murine-model experiments
Strengths:
- Developed method for evaluating candidate cardiac therapies
Weaknesses:
- Low awareness of gene therapy-based treatments and legislation difficulties facing regenerative medicine
- Scarcity of in vitro human model systems for evaluation of putative gene therapy-based treatments
Patent Status:
- Priority date: 2015-03-02
- Filing date: 2016-09-09
Publications:
- Addis RC, Ifkovits JL, Pinto F, Kellam LK, Esteso P, Rentschler S, Christoforou N, Epstein JA, and Gearhart JD. (2013) Optimization of Direct Fibroblast Reprogramming to Cardiomyocytes using Calcium Activity as a Functional Measure of Success. JMCC (in press)
- Rentschler S, Yen AH, Lu J, Petrenko NB, Lu MM, Manderfield, LJ, Patel VV, Fishman GI, Epstein JA. (2012). Myocardial Notch Signaling Reprograms Cardiomyocytes to a Conduction-Like Phenotype. Circulation, 126(9):1058-66. PMCID: PMC3607542
- Manderfield L, High F, Engleka K, Liu F, Li L, Rentschler S, Epstein JA. (2012). Notch Activation of Jagged-1 Contributes to the Assembly of the Arterial Wall. Circulation, 125(2):314-23. PMCID: PMC3260393
- Rentschler S, Harris BS, Kuznekoff L, Jain R, Manderfield L, Lu M, Morley GE, Patel VV, Epstein JA. (2011). Notch Signaling Regulates Murine Atrioventricular Conduction and Formation of Accessory Pathways. Journal of Clinical Investigation, 121(2):525-33. PMCID: PMC3026731
- Jain R, Engleka KA, Rentschler S, Yuan L, Li L, Epstein JA. Cardiac Neural Crest Orchestrates Remodeling and Functional Maturation of the Semilunar Valves. (2011). Journal of Clinical Investigation, 121(1):422-30. PMCID: PMC3007154
- Rentschler S and Epstein JA. (2011). Kicking the Epicardium up a Notch. Circulation Research, 108(1):6-8.
- Jain R, Rentschler S, Epstein JA. (2010). Notch and Cardiac Outflow Tract Development. Annals of the New York Academy of Sciences, 1188:184-90 PMCID: PMC2975619
- Rentschler S, Jain R, Epstein JA. Tissue-Tissue Interactions During Morphogenesis of the Outflow Tract. (2010). Pediatric Cardiology, 31(3):408-13 PMCID: PMC2951316
- Rentschler S, Zander J, Burns K, France D, Levine R, Porter G, Rivkees SA, Morley GE, Fishman GI. (2002). Neuregulin-1 promotes formation of the murine cardiac conduction system. Proceedings of the National Academy of Science, 99:10464-9. PMCID: PMC124940
- Rentschler S, Vaidya DM, Tamaddon H, Degenhardt K, Sassoon D, Morley GE, Jalife J, Fishman GI. (2001). Visualization and functional characterization of the developing murine cardiac conduction system. Development, 128:1785-92.
Inventor Bio: Stacey Rentschler
https://cardiovascularresearch.wustl.edu/labs/stacey-l-rentschler-md-phd/
