Non-surgical Heart Valve Replacement, Preventing Strokes, Concussions, Epilepsy and Autism, Cancer Research Awards

mccannn [at] email.chop.edu (By Nancy McCann)

In this week’s roundup of research news, read about Children’s Hospital of Philadelphia’s role in the Food and Drug Administration-approved device for non-surgical heart valve replacement and a common supplement that may reduce the risk of fatal strokes caused by a rare genetic disorder. Learn which sports put students at the highest risk for head impacts that could lead to concussions, the implications of mapping the clinical landscape of a major gene linked to epilepsy and autism, and who among us received awards to accelerate childhood cancer research.

FDA Approves Non-surgical Heart Valve Replacement Device

Matthew Gillespie, MD

CHOP was the lead enrolling site in the clinical trial that led to the approval of the Harmony™ Transcatheter Pulmonary Valve (TPV). This medical technology advancement allows for pulmonary valve replacement via a minimally invasive catheter-based procedure. The device consists of a self-expanding metal frame combined with valve leaflets that can be implanted inside a patient’s heart.

“The approval of this device will allow us to provide a non-surgical option to patients with congestive heart disease, reducing or eliminating the need for multiple open heart surgeries over the course of a patient’s lifetime,” said CHOP site PI, Matthew Gillespie, MD, interventional cardiologist in the Cardiac Center, director of CHOP’s Cardiac Catheterization Laboratory, and co-director of its Center for Pediatric Heart Valve Disorders. “Researchers in the Cardiac Center at CHOP are committed to bringing our expertise to the development of cutting-edge treatments, which will improve the lives of our patients and their families.”

Read more in the press release.

Nutritional Supplement Prevents Strokes in Patients With Rare Genetic Disorder

Hakon Hakonarson, MD, PhD

Researchers in CHOP’s Center for Applied Genomics discovered that a widely used nutritional supplement called N-acetyl-cysteine (NAC), may significantly reduce the risk of fatal strokes caused by a rare genetic disorder known as hereditary cystatin C amyloid angiopathy (HCCAA). The findings also suggest that the supplement could be used to both block precipitation of and break up the formation of amyloid plaque deposits, a common feature found in serious forms of dementia. Nature Communications published the researchers’ findings.

HCCAA is part of a group of diseases in which amyloid proteins build up, and deposits form on the walls of blood vessels in the central nervous system. Most people with this disorder suffer strokes and brain hemorrhages in their 20s that become more frequent, leading to paralysis, dementia, and death. The amyloid deposits observed in cases of HCCAA are implicated in a wide range of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington´s diseases.

“While this is a rare disease, most patients diagnosed with HCCAA die within five years of their first stroke, so there is an incredible need to study this genetic disorder and find effective treatment options,” said senior author Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics.

“Amyloids cannot precipitate without aggregating, so if we can prevent that aggregation with a drug that is already available, then we could make an incredible difference in the lives of these patients,” Dr. Hakonarson said. “Additionally, since we already have genetic testing available to identify these patients, we could conceivably give this treatment early in life and potentially prevent that first stroke from ever occurring.”

Go to CHOP News for study details.

Using Sensors, Researchers Identify Head Impact Rates in Four High School Varsity Sports

Kristy Arbogast, PhD

Researchers in CHOP’s Center for Injury Research and Prevention used head impact sensors in four different high school varsity sports — soccer, basketball, lacrosse, and field hockey — and studied male and female athletes to determine which of these sports put students at the highest risk for head impacts that could lead to concussions. The Orthopaedic Journal of Sports Medicine published the findings.

The study team collected data from 124 athletes (56 girls, 68 boys) over the course of 104 games and more than 1,600 head impacts across the four sports. Soccer had the highest head impact rate for both boys and girls and was attributed to the role of intentional headers, which accounted for 80 percent of the head impacts in that sport. High school male sports consistently had higher head impact rates than female sports in soccer, basketball, and lacrosse.

“Adolescents are particularly vulnerable to concussion because they frequently participate in sporting and recreational activities and have slower recovery periods compared to adults,” said lead author Kristy Arbogast, PhD, co-lead of the Minds Matter Concussion Program at CHOP. “Providing reliable data on head impact exposure and sport-specific mechanisms may help sports organizations identify strategies to reduce impact exposure and lower the risk of acute injury.”

To learn more, read this Healio article or go to CHOP News.

Researchers Map Clinical Landscape of Major Gene Linked to Epilepsy and Autism

Ingo Helbig, MD

CHOP researchers, including several with the CHOP Epilepsy Neurogenetics Initiative (ENGIN), compiled a complete genetic and clinical analysis of more than 400 individuals with SCN2A-related disorder, which has been linked to a variety of neurodevelopmental disorders, including epilepsy and autism. By associating clinical features to genetic abnormalities in a standardized format, using a method called Human Phenotype Ontology (HPO), the researchers hope their findings inform improved identification and clinical intervention. Genetics of Medicine published the findings.

“The SCN2A-related disorders are the first group of conditions where such a systematic mapping to computable phenotypes was performed,” said senior author Ingo Helbig, MD, pediatric neurologist in the Division of Neurology and a core faculty member of ENGIN. “Our findings help define subclasses within SCN2A-related disorders that could pave the way for future precision medicine approaches to help these individuals. This work, built upon our previous studies, now provides a framework on how HPO terminology can map complex clinical data in a variety of rare disorders to get to answers about clinical features, natural history, and outcomes that we do not have yet.”

Learn more in this CHOP press release.

CHOP Researchers Receive Grants to Accelerate Childhood Cancer Research

Kathrin Bernt, MD

Richard Aplenc, MD, PhD, MSCE

We’re proud to announce Kathrin Bernt, MD, and Richard Aplenc, MD, PhD, MSCE, are recipients of the Accelerating Impact for Hard to Treat Cancers Awards from the Children’s Cancer Research Fund. These funds support researchers focused on the most pressing needs, including development of new therapies for hard-to-treat cancers and unlocking access to shared data.

Dr. Bernt’s research project is titled “Targeting MN1 in Hard-To-Treat Cancer.” Meningioma-1 (MN1) is a protein whose overexpression has been linked to acute myeloid leukemia (AML), the second most common blood cancer in children, as well as brain tumors. Over 70 percent of AML patients with high overexpression of MN1 die within two years, yet the mechanism by which MN1 causes these diseases has largely remained a mystery. By building on the promising findings of her recent MN1 study (soon to be published), Dr. Bernt aims to turn her research into a therapy.

The research project of Dr. Aplenc, assistant vice president and chief clinical research officer of CHOP’s Research Institute, also focuses on AML. The title of his grant is “Proteogenomic Target Discovery in Pediatric Acute Myeloid Leukemia,” and is a joint collaborative endeavor with Yi Xing, PhD, director of CHOP’s Center for Computational and Genomic Medicine. Drs. Aplenc and Xing will generate proteomic and RNA-seq data that will be interrogated and integrated to identify novel targets for AML therapy.

ICYMI

Catch up on our headlines from our March 19 In the News:

• AIMBE Inducts Hao Huang, PhD, as Fellow
• HERO Registry Highlights COVID-19’s Impact on Healthcare Workers
• CHOP Researchers Awarded ALSF Crazy 8 Grant
• Targeted Treatment Shows Benefit for High-Risk B-ALL
• Study Describes How Key Lung Part Forms at the Cellular Level

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