Sleuthing the Cause of Cardiomyopathy
Applying What We’ve Learned
Dr. Stephanie Ware is a research scientist in the Division of Molecular Cardiovascular Biology, a clinical geneticist in the Division of Human Genetics and co-director of the Diagnostic Cardiomyopathy Clinic at Cincinnati Children’s. She is an assistant professor in the Department of Pediatrics at the University of Cincinnati College of Medicine.
Read more about Dr. Ware’s work.
Despite advances in understanding adult heart muscle disease, much about its causes in children remains a mystery. Stephanie Ware, MD, PhD, a researcher with appointments in the Division of Molecular Cardiovascular Biology and the Division of Human Genetics, is looking to change that, with some high-tech assistance. Dr. Ware and her team are using a nextgeneration high throughput gene sequencer to splice and dice children’s blood samples into their most fundamental bits. The genetic
codes that result may well carry the clues to why a child develops heart disease.
A First-Time Endeavor
With the help of the super sequencer, Dr. Ware and her team will analyze enormous amounts of DNA from small samples of blood. It will be the first time ever that researchers have examined the genetic makeup of a large number of children with cardiomyopathy. Dr. Ware hopes it will provide answers to questions that have been perplexing doctors for years.
“Are children different from adults in terms of the genes that are important? Or in some children, is there more than one gene causing disease? These types of studies haven’t been done before in children,” she says. “It’s not yet understood why, in some families, many of the people don’t develop cardiomyopathy until they’re adults, but they’ll have a child born with cardiomyopathy, or diagnosed with it soon after birth. It’s not clear why it’s so severe in one child in the family. That speaks
to the lack of a comprehensive assessment.”
Dr. Ware and her team will focus on genes responsible for energy production, heart muscle contraction and the structure of the heart muscle cell. Ultimately, their goal is to find better treatments.
“Right now children with cardiomyopathy or heart failure are all treated the same way – and some kids respond well and some don’t,” Dr. Ware says. “If they don’t respond well to medical management, they go to heart transplant. “
Getting Personal
By understanding the genetic basis, Dr. Ware and her team hope to identify treatments that can be precisely targeted to an individual child’s heart problem. “We think that a patient who has a genetic defect that causes her heart muscle to be abnormal is going to be very different from the patient who has a problem with mitochondria and energy production, where the heart muscle is normal, it’s just not getting the energy it needs.”
The process of analyzing the samples is already underway. Dr. Ware and her team currently have 100 blood samples collected by investigators at other institutions and they are preparing the DNA for high-throughput sequencing. She believes this will be a solid foundation to build on with blood samples from current and future patients at Cincinnati Children’s.
Connecting Symptom to Cause
The researchers hope their analysis will show patterns that correlate with clinical symptoms – how and at what age the patients presented; what type of cardiomyopathy they have.
“The heart has a variety of ways it can choose to show its dysfunction. We’re thinking that those different ‘flavors’ of clinical presentation may correlate with specific genetic defects,” Dr. Ware explains. “We’ll include those different flavors and age ranges in this pilot study and hope that we’ll see patterns that will make us a little smarter in the second round of ‘what do we need to look at in this age range, with this type of
heart failure?’”
Where heart disease runs in the family, Dr. Ware believes her team can identify genes that cause the disease, as well as those that may help explain why it is more severe in a child than in a parent. In cases where there is no family history, they will explore whether the genetic causes are the same, or whether there are other genes that need to be investigated.
The findings should provide valuable information where little or none exists. “In pediatric cardiomyopathy, we really have a lack of knowledge about the genetic basis,” Dr. Ware says. “Nobody in the country has taken this comprehensive look before, looking at large numbers of genes in a large number of patients.”
We’re at a very basic level of fact finding. We can’t do much from a management or therapy standpoint until we understand the actual causes. I think really exciting research will happen after we get past this first phase.”
