Thursday, March 6, 2014
A U.S. team has found a way to harness the
cardioprotective activity of tissue inhibitor of metalloproteinases 3
while avoiding its off-target effects by embedding it in a hydrogel for direct
injection into the heart.1 Although preclinical data show that local
delivery of the molecule could help prevent heart failure after myocardial
infarction in patients with ventricular dilation, it may have a detrimental
effect in other patients, making patient selection critical.
Straight to the heart
The team encapsulated recombinant TIMP3 (rTIMP3)
in a biodegradable hyaluronic acid gel and obtained slow
release of rTIMP3 in vitro that maintained a uniform release profile for
at least 14 days.
According to Lindsey, the localized hydrogel delivery
system should minimize the risk of off-target effects.
Florence Pinet told SciBX that current treatments-which
include acute reperfusion strategies and anti-remodeling medications such as angiotensin-converting enzyme
(ACE) inhibitors and b-blockers-do not prevent ventricle
remodeling in about 30% of patients.
Martz, L. SciBX 7(9);
Published online March 6, 2014
1. Eckhouse, S.R. et
al. Sci. Transl. Med.; published online Feb. 12, 2014;
Contact: Francis G. Spinale, University of South Carolina School of
Medicine, Charleston, S.C.
2. Dormán, G. et al.
Drugs 70, 949-964 (2010)
3. Kassiri, Z. et al.
J. Biol. Chem. 284, 29893-29904 (2009)
4. Mukherjee, R. et al.
Ann. Thorac. Surg. 86, 1268-1276 (2008)
Albert Einstein College of Medicine of Yeshiva University, New York, N.Y.
(NASDAQ:AMGN), Thousand Oaks, Calif.
Institut National de la Sante et de la Recherche Medicale, Lille, France
LoneStar Heart Inc., Laguna Hills, Calif.
San Antonio Cardiovascular Proteomics Center, San Antonio, Texas
The University of Mississippi Medical Center, Jackson, Miss.
University of Pennsylvania, Philadelphia, Pa.
University of South Carolina School of Medicine, Columbia, S.C.
The University of Texas Health Science Center at San
Antonio, San Antonio, Texas
San Diego, Calif.