Details

Project TitleHeart Disease Therapy by Regulation of the Mitochondrial Calcium Uniporter
Track Code2013-013
Short Description

Researchers at the University of Iowa have developed a new therapy to treat and prevent heart disease. First, they showed that CaMKII stimulates mitochondrial calcium uniporter to promote mitochondrial pore opening, increasing calcium influx and myocardial death. In mice with myocardial and mitochondrial-targeted CaMKII inhibition, mitochondrial calcium entry is reduced and these animals are resistant to ischemia reperfusion injury, myocardial infarction and neurohumoral injury. Second, the researchers developed biodegradable nanoparticles to deliver CaMKII inhibitors to the mitochondria. Polyamidoamine (PAMAM) dendrimers and/or polylactic-co-glycolic acid (PLGA) are used to make submicron-sized nanoparticles. Included in the nanoparticle are a mitochondria localization sequence, or a mitochondrial targeting moiety, triphenylphosphonium cation (TPP), to facilitate targeting CaMKII inhibitor to the mitochondria. Nanoparticle-encapsulated CaMKII inhibitor protected cardiac cells against ischemia/reperfusion injury.

Abstract

Background 

Heart disease is the leading cause of death in the United States, affecting 1 in 16 adults and costing the United States' economy $444 billion annually. A major cause of heart disease is myocardial cell death. Myocardial cell death is associated with the dysregulation of mitochondrial calcium transport particularly the activation of calcium/calmodulin-dependent protein kinase II (CaMKII). CaMKII is activated in ischaemia reperfusion, myocardial infarction and neurohumoral injury common causes of myocardial death and heart failure. This suggests that CaMKII is an ideal cellular target for intervention against heart disease. 

 Technology Summary 

Researchers at the University of Iowa have developed a new therapy to treat and prevent heart disease. First, they showed that CaMKII stimulates mitochondrial calcium uniporter to promote mitochondrial pore opening, increasing calcium influx and myocardial death. In mice with myocardial and mitochondrial-targeted CaMKII inhibition, mitochondrial calcium entry is reduced and these animals are resistant to ischemia reperfusion injury, myocardial infarction and neurohumoral injury. Second, the researchers developed biodegradable nanoparticles to deliver CaMKII inhibitors to the mitochondria. Polyamidoamine (PAMAM) dendrimers and/or polylactic-co-glycolic acid (PLGA) are used to make submicron-sized nanoparticles. Included in the nanoparticle are a mitochondria localization sequence, or a mitochondrial targeting moiety, triphenylphosphonium cation (TPP), to facilitate targeting CaMKII inhibitor to the mitochondria. Nanoparticle-encapsulated CaMKII inhibitor protected cardiac cells against ischemia/reperfusion injury.

 
Tagsmitochondrial calcium uniporter
 
Posted DateJun 6, 2017 4:22 PM

Licensing Contact

Kenneth Karanja, PhD

Licensing Associate,

University of Iowa Research Foundation,

2660 University Capital Center,

Iowa City, IA 52242.

Email: kenneth-karanja@uiowa.edu

Tel: 319-335-4607

University of Iowa Research Foundation

Files

File Name Description
2013-013 Technology Summary.pdf None Download