Precision medicine may hold key to improving pediatric HF outcomes
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Emerging precision medicine therapies targeting the molecular causes of cardiomyopathy and HF may improve the outlook for pediatric patients with HF, according to a review published in Translational Pediatrics.
“A lot of times, pediatric medicine [consists of] extrapolating data from adult studies and trying to apply adult medicine to pediatrics,” Aryaz Sheybani, MD, attending physician in pediatric heart failure and heart transplantation, Nemours Children’s Hospital, Delaware, told Healio. “As we are getting better genetic studies and better understanding of the basis of disease, there are more therapies that we are trying to use at a younger age to be preventive. We were looking at some of those that are tailored to specific genetic defects at a younger age to prevent heart failure and sometimes to reverse the course of heart failure after it started. With cascade screening, if we are able to identify families at risk with certain mutations, then we can start therapies before some children have shown disease.”
To compile the review, Sheybani and colleagues assessed studies published between January 2000 and August 2022 regarding the genetic basis and treatment modalities of pediatric HF.
‘A unique position’
“Pediatric providers are in a unique position to begin therapies before significant pathology has developed, and it will be of crucial importance for the pediatric clinician to keep abreast of this rapidly evolving reality of precision medicine that will dictate care for their patients,” the researchers wrote.
Sheybani said a major development in treatment of HF and cardiomyopathy in pediatric patients has been the formation of the multicenter ACTION network, a collaborative to launch studies in ventricular assist devices, Duchenne muscular dystrophy, Fontan circulation and related fields.
He also cited work with cardiosphere-derived cell therapies that could potentially “give cells to hearts that aren’t yet failing, but are at risk of failing, and preserve their function.” So far, work has mainly centered on patients with single-ventricle syndromes in Japan, but research of these therapies for other forms of cardiomyopathy has begun, he said.
Better understanding of genetic defects, particularly factors such as whether they are gain-of-function or loss-of-function, will further help develop treatments in this area, Sheybani told Healio.
Knowing the effect of these mutations will help in defining therapies, he said, citing work in patients with Noonan syndrome, where patients with a gain-of-function mutation in the RAS/MAPK signaling pathway have been shown to be amenable to treatment with trametinib (Mekinist, Novartis), an MEK inhibitor.
‘Some degree of benefit’
“Nobody has a large experience with it at this point, but most of us have had at least a couple of patients treated with trametinib and seen some degree of benefit,” Sheybani told Healio.
Another area of research is therapies targeting the underlying dystrophin deficiency in patients with Duchenne muscular dystrophy, he said, noting that one, ataluren (Translarna, PTC Therapeutics), has been conditionally approved in Europe.
“It is a very exciting time right now, as we get a better understanding of the genetic basis of disease, where pediatrics is positioned to finally make changes before [adult medicine],” Sheybani told Healio. “We are truly in a spot where we can predict and prevent disease for many patients. The possibility of having one medication that is tailored to a patient’s disease instead of three or four for heart failure, having a normal quality of life without cardiac dysfunction, is probably several years off, but we are getting much closer.”
For more information:
Aryaz Sheybani, MD, can be reached at Nemours Children's Hospital, Delaware, 1600 Rockland Road, Wilmington, DE 19803.
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