London, Canada
Researchers at the University of Western Ontario have published a paper in the October 15th, 2006, issue of the Journal of Cell Sciences (Karamboulas C et al, HDAC activity regulates entry of mesoderm cells into the cardiac muscle lineage. J Cell Sci. 2006 Oct 15;119(Pt 20):4305-14) describing mechanisms by which inhibition of histone deacetylases induces differentiation of mesodermal cells into cardiomyocytes.
The paper describes that treatment of the P19 cell line-derived mesodermal aggregates with trichostatin A (inhibitor of histone deacetylases) induces cardiomyocyte differentiation through upregulation of the transcription factors GATA4 and Nkx2-5.
Trichostatin A (TSA), is an antifungal antibiotic that has been extensively used in animal models for treating diseases ranging from cancer to autoimmunity. Currently under development are novel analogues of TSA. This paper suggests that it may be possible to use histone deacetylase inhibitors in the area of regenerative medicine and provides a molecular mechanism for its function.
The use of histone deacetylase inhibitors for cardiac treatment purposes is described in US patent # 6,946,441 to Long; Carlin et al entitled Inhibition of histone deacetylase as a treatment for cardiac hypertrophy. This patent is assigned to the Regents of the University of Colorado, A Body Corporation (Boulder, CO) and The Board of Regents, The University of Texas System (Austin, TX). It was issued September 20, 2005. This patent has 1 independent claim which covers treatment of heart failure by administration of a histone deacetylase inhibitor. One of the dependent claims covers the use of trichostatin A, trapoxin B, MS 275-27, m-carboxycinnamic acid bis-hydroxamide, depudecin, oxamfiatin, apicidin, suberoylanilide hydroxamic acid, Scriptaid, pyroxamide, 2-amino-8-oxo-9,10-epoxy-decanoyl, 3-(4-aroyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamide and FR901228 for these purposes.
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