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SciBX: Science–Business eXchange Copyright © 2008 Nature Publishing Group �

This week in therapeutics

Indication
Target/marker/
pathway Summary Licensing status

Publication and contact  
information

Cardiovascular disease

Left ventricular 
hypertrophy (LVH)

G protein–coupled 
receptor kinase 5 
(GRK5); guanine 
nucleotide 
binding protein, 
q polypeptide 
(GNAQ; Gq); 
histone deacetylase 5 
(HDAC5); myocyte 
enhancing factor 2 
(Mef2; D-Mef2)

Studies in mice and in cell culture suggest that 
targeting GRK5 could help treat LVH associated 
with heart failure. In mouse models of pressure-
overload cardiac stress, GRK5 overexpression led 
to cardiac hypertrophy and increased the incidence 
of heart failure compared with what was seen in 
wild-type mice or mice that overexpressed a GRK5 
variant that did not enter the nucleus. 
In vitro, cardiac stress–induced G protein–coupled 
receptor signaling led to upregulation of GRK5 
and its subsequent translocation to the nucleus, 
where it induced HDAC5-mediated expression of 
hypertrophy genes. Ongoing studies will assess the 
specificity of GRK5’s activation of HDAC5 and the 
effects of targeting GRK5 with a GRK5-specific 
microRNA. 
Many companies market or are developing 
compounds to treat or prevent hypertrophy via 
treatment of hypertension and/or ischemia, two 
conditions that can lead to LVH and subsequent 
heart failure. 

Not patented; 
licensing status 
undisclosed

Martini, J. et al. Proc Natl. Acad. Sci. 
USA; published online Aug. 4, 2008; 
doi:10.1073/pnas.0803153105 
Contact: Walter J. Koch, 
Thomas Jefferson University, 
Philadelphia, Pa.  
e-mail: 
walter.koch@jefferson.edu

http://www.scibx.com
mailto:walter.koch@jefferson.edu

	G protein–coupled receptor kinase 5 (GRK5); guanine nucleotide binding protein, q polypeptide (GNAQ; Gq); histone deacetylase 5 (HDAC5); myocyte enhancing factor 2 (Mef2; D-Mef2)
	Summary
	Licensing Status
	References