Advances and Answers in Pediatric Health
ventricle hearts have dysregulated metabolic pathways and impaired mitochondrial function . They also found an intermediate metabolic phenotype in single ventricle hearts prior to the onset of heart failure , suggesting even nonfailing single ventricle hearts are vulnerable to metabolic dysfunction and eventual heart failure ( 1 ).
SUPPORTING THE RESEARCH
These kinds of studies are possible thanks to the cardiac tissue biobank on the CU Anschutz Medical Campus . This is an essential tool for pediatric researchers studying heart failure because they are not able to conduct many of the invasive studies researchers perform to study heart failure in adults , such as heart muscle biopsies . Once a child needs a heart transplant , the researchers get permission from the families to take part of the diseased heart for this biobank . The challenge with mitochondrial studies like the one Drs . Miyamoto and Garcia have been working on is timing .
“ These mitochondrial studies have to be done in the moment , because once you freeze the mitochondria , they burst and they aren ’ t going to function anymore ,” Dr . Miyamoto says . “ Some of these studies need to be done in the middle of the night or the middle of the week . If it ’ s Christmas Day , it ’ s done on Christmas Day .”
Once the team is notified that a heart transplant is taking place , they spring into action to complete their mitochondrial studies immediately . They then freeze the rest of the heart tissue to study later .
“ That freezes that piece of tissue in time . So , it preserves things like enzymes , proteins and genes so we can go back and look later ,” Dr . Miyamoto says .
IDENTIFYING PROMISING THERAPEUTIC TARGETS
With this understanding of the mitochondria ’ s role in heart failure for single ventricle patients , Drs . Miyamoto and Garcia and their team have turned to studying different , promising therapeutic options that target the mitochondria ’ s function .
“ This is highly impactful , because there are now drugs that target the mitochondria ,” Dr . Miyamoto explains . “ If this is one of the reasons the heart is failing , then there are therapies that can target that mitochondria and hopefully help the mitochondria function better .”
Along with their collaborator , Denver Health ’ s head of cardiology Brian Stauffer , MD , Drs . Miyamoto , Garcia and Chatfield have identified the drug elamipretide ( which is not yet FDA approved for any indication in the U . S .) as a helpful option to improve mitochondrial function in a failing heart . In addition to this drug , Dr . Miyamoto ’ s current R01 grant is looking into a drug called sildenafil , which could also improve mitochondrial function in this population .
“ We need to think about different targets of therapy and identifying different drugs that work in our [ pediatric ] population and not just assume that all these drugs that are great for adults with heart failure are going to help children ,” Dr . Miyamoto says .
The location of Children ’ s Colorado on a major medical campus with researchers studying the entire lifespan on all corners of campus offers a unique opportunity for collaboration . Dr . Miyamoto says all this work would not be possible without the valuable collaboration with adult cardiology colleagues on the CU Anschutz Medical Campus who started this group with her back in 2007 : Kika Sucharov , PhD , a molecular biologist , and Dr . Stauffer . Dr . Chatfield is also on the pediatric team as one of Dr . Miyamoto ’ s mentees , and she is an expert in cardiac genetics and mitochondrial function , who plays a key role in bringing these research studies to life . She has also been essential to the team ’ s research on the drug elamipretide and mitochondrial function over the years .
ADVANCING DISCOVERY WITH A MULTIFACETED APPROACH
Pediatric cardiologist Dr . Nakano collaborates closely with Drs . Miyamoto and Garcia and is continuing to push this research forward with a $ 2.4 million award from the Department of Defense ( DOD ) to study a specific kind of single ventricle heart disease ,
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