Gene Targets in Anti-aging Therapy and Tissue Repair
Joshua Hare and Bettina Heidecker
Problem
There is an urgent need for improved efficacy in currently applied cell therapeutic approaches in regenerative medicine.
Solution
Therapeutic target genes could play a fundamental role in cell based therapy in patients with heart failure. Specifically, targeted gene therapy may increase the viability of injected stem cells that are used for cardiac repair. The pathways may also have direct therapeutic utility and may be manipulated by gene therapy or by a small molecule approach. This application of specifically designed stem cells may be expanded to many fields in medicine.
Competitive Advantage
While various types of cell therapy, such as mesenchymal or embryonic stem cells, have been successfully applied in organ regeneration, there has not been agreement on the optimal type of cell. Furthermore, the question rises if cells should be modified to increase their survival after implantation into the diseased organ and to enhance their therapeutic potential. RAD50 and SMG6 may be important targets for gene therapy that seek to enhance stem cell efficacy in organ failure and tissue repair.
Applications
Given that the presence and regenerative capacity of stem cells has been proven in numerous organ systems, specific gene therapy or small molecule approach as a tool to enhance RAD50 and SMG6 expression levels may find broad application in regenerative therapy.
Patent Status
International Patent Application No.
WO2009033162
entitled "GENE TARGETS IN ANTI-AGING THERAPY AND TISSUE REPAIR," was published March 12, 2009.
Licensing Opportunity
The University of Miami is seeking collaborative research and licensing options.
About the Inventors
Dr. Joshua Hare was recruited from Johns Hopkins University to become chief of cardiology and director of the Interdisciplinary Stem Cell Institute at the University of Miami. Trained at Harvard and Johns Hopkins Hospital, he became a highly productive scientist in the field of heart failure and cardiomyopathies, contributing an enormous amount of work in basic science and clinical research (1-4). Over many years, Dr. Hare and his laboratory have placed a major focus on transcriptomic biomarker research (4-7), with the ultimate goal to improve diagnostic and prognostic accuracy in heart failure. In fact, his group published the first proof-of-concept study that transcriptomic biomarkers are feasible in cardiology and can be used to differentiate between the two major forms of cardiomyopathy, ischemic and non-ischemic (4).
Dr. Bettina Heidecker came with Dr. Hare and his team from Hopkins. She conducted her medical thesis on autoimmune mechanisms and heat shock proteins in atherosclerosis in Dr. Georg Wick's laboratory in Innsbruck, Austria. After graduation with her M.D., she started as a Post-Doctoral Fellow in Dr. Hare's group and specialized in microarray analysis and transcriptomic biomarkers. Together with Dr. Hare, she successfully developed a transcriptomic biomarker for the prediction of long-term clinical outcomes in patients with new onset heart failure and detection of myocarditis from a single endomyocardial biopsy. Furthermore, each biomarker revealed important targets for gene or cell therapy. For this work, she was awarded the Samual A. Levine Clinical Young Investigators Award from the American Heart Association and a grant from the Wallace H. Coulter Center. The novel biomarkers are currently validated in a clinical trial involving 150 patients, which will also elucidate if blood cells can be used as a surrogate for heart biopsies (8, 9).
Selected References
(1) Barouch LA, Harrison RW, Skaf MW et al. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 2002 March 21;416(6878):337-9.
(2) Amado LC, Saliaris AP, Schuleri KH et al. Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci U S A 2005 August 9;102(32):11474-9.
(3) Gonzalez DR, Beigi F, Treuer AV, Hare JM. Deficient ryanodine receptor S-nitrosylation increases sarcoplasmic reticulum calcium leak and arrhythmogenesis in cardiomyocytes. Proc Natl Acad Sci U S A 2007 December 18;104(51):20612-7.
(4) Kittleson MM, Ye SQ, Irizarry RA et al. Identification of a gene expression profile that differentiates between ischemic and nonischemic cardiomyopathy. Circulation 2004 November 30;110(22):3444-51.
(5) Hare J.M. The dilated, restrictive and infiltrative cardiomyopathies. In: Zipes DP, Libby P, Bonow R, Braunwald E, editors. Braunwald's Heart Disease. 8 ed. Elsevier; 2007.
(6) Heidecker B, Hare JM. The use of transcriptomic biomarkers for personalized medicine. Heart Fail Rev 2007 March;12(1):1-11.
(7) Kittleson MM, Irizarry RA, Heidecker B, Hare J.M. Transcriptomics: Translation of Global Expression Analysis to Genomic Medicine. In: Willard H.F., Ginsburg G.S., editors. Handbook of Genomic Medicine. 1st ed. Elsevier; 2008.
(8) Deng MC, Eisen HJ, Mehra MR et al. Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling. Am J Transplant 2006 January;6(1):150-60.
(9) Liew CC, Ma J, Tang HC, Zheng R, Dempsey AA. The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 2006 March;147(3):126-32.
