Presentation 60,61
Presentation 60
Injection of Novel Cross-Linked Alginate Solution Attenuates Solution Attenuates Infarct Expansion and Preserves Left
Ventricular Systolic and Diastolic Function Late After Myocardial Infarction.
Leah N Klapper(1), Shmuel Tuvia(1), llan Winkler(1), Hanna Ron(1), Mazal Shaul(1), Kinneret Livnat-Savitsky(1), Smadar Cohen(2), Jonathan Leor(3).
(1) Biolone RX Ltd
(2) Neufeld Cardiac Research Institute, Sheba Medical Center
(3) Faculty of engineering sciences, Ben-Gurion University
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Cessation or reversal of progressive left ventricular (LV) dysfunction is a major aim of heart failure therapy. We developed a cross-linked concentrated alginate solution (BL-1040), which upon solidification in tissue becomes an hydrogel. The aim of the present study was to test the hypothesis that an injection of this novel alginate solution mimicking the extracellular matrix (ECM) into an old scar tissue, late after myocardial infarction (Ml), will provide physical and biological scaffolding, promote tissue rejuvenation and will prevent progressive LV dysfunction.
Injection of biodegradable alginate biomaterial into the infarcted myocardium of rat improves scar thickness and attenuates LV dilatation and dysfunction. In a rat model of old infarction and chronic heart failure, we showed, for the first time, that injection of in situ gelling solution of crossed-link alginate into an old scar tissue provides physical and biological scaffolding, and preserves LV systolic and diastolic function. In a pig model of ischemia reperfusion, we show, for the first time, the safety, efficacy and tissue distribution of injectable alginate solution delivered by percutaneous catheter-based intra-coronary approach, into the infarcted heart. Histological findings confirm effective delivery and distribution and suggest myocardial regeneration.
Our work enables a minimally invasive, catheter-based, acellular option to repair new and old scar tissue and to treat Ml and prevent heart failure.
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Presentation 61
Excitable tissue Electrophysiological Modification By Fibroblasts Overexpressing lon Channels : A Novel Approach For The Treatment Of Cardiac Arrhythmias And Neurological Disorders
Z Gluzman(1), T Bresler(1), R Miary(1), L Gerion(1), M Reshef(1), M Boulos(2),L Yankelson(3), J Finberg(3), L Gepstein(3), S Marom(3), Y Feld(1)
(1)Gene Grafts Ltd
(2)Unit for electrophysiology, Rambam Medical Center
(3)Dept of Physiology, Technion - Israel Institute of Technology
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GeneGrafts is a biotech start-up company developing treatment for cardiac arrhythmias and neurological disorders by transplantation of autologous cells expressing ion channels. Currently the company has decided to focus on developing treatment for atrial fibrillation (AF) and Parkinson's disease. Modern AF treatments are primarily supportive and limited to pharmacotherapy, radiofrequency ablation, or implantable devices. About 12% ofAF sufferers or 275,000 people in the U.S. have severe and refractory AF.
Using its somatic cell therapy technology platform GeneGrafts is developing a rate control therapy for AF. So far GeneGrafts has demonstrated in in-silico, in-vitro, and in-vivo studies that cell grafts overexpressing ion channels can electrically couple with cardiac myocytes, and cause a local and reversible modification of a tissue's electrophysiological properties. The feasibility and safety of endocardially cell targeting and injecting the AV node was approved and appears as safe method for cell administration into the AV node. The ability of fibroblasts, over expressing the specific potassium channel gene to modulate the ventricular response rate after being endocardially injected to the AV node was demonstrated as well. The refractory period of the AV node was prolonged as a result of the cell injection.
Additionally the Company has demonstrated improvement in ventricular response during AF in pig hearts. GeneGrafts also demonstrated neurological discharge modification in vitro and improvement in rotational behavior in Parkinsonian rats. Based on these proof-of-concept studies, the Company proceeds to the toxicological studies and plans to complete Phase I trials forAF and Parkinson's disease by Q1 2008 and Q1 2009 respectively.
