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New Rare Disease, FA Woodstock, Bioengineering, and Protecting Toddlers from Child Abuse

Published on July 29, 2016 in Cornerstone Blog · Last updated 4 months 1 week ago


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Welcome back to another weekly edition of our roundup of research news from The Children’s Hospital of Philadelphia! One of the things that is so exciting about research at CHOP is that our researchers are working to improve the health and lives of children in such a broad range of ways. This week’s stories give a glimpse of that breadth, from reaching out to a rare-disease community of families at a grassroots festival, to bioengineering a molecule that could rapidly stop dangerous excess bleeding, to identifying a new rare syndrome caused by a genetic flaw in a fundamental cellular process, to developing evidence-based guidelines to consistently protect more infants and toddlers from child abuse. Read on for the details.

Families Retreat for Research and Camaraderie at “FA Woodstock”

An outdoor family festival unlike any other brought visitors from far-flung international destinations to a ranch in rural Indiana for three days earlier this month. The attendees all had one thing in common: They, or members of their families, have Friedreich's ataxia (FA) a rare, progressive neurogenetic condition that affects the function of the cerebellum, the part of the brain that helps plan and coordinate movements.

The event, dubbed “FA Woodstock,” is a grassroots festival organized by hosts Tom and Paula Hook, whose daughter Kati has FA, at their home ranch. A major focus of the weekend is relaxation and camaraderie so that families can connect and feel less lonely in their dealings with a rare disease.

But a gathering of so many individuals with a rare disease and their families has another major benefit: research.

“The main reason why clinical trials fail in rare diseases is because you don’t find enough subjects,” David Lynch, MD, PhD, told the Washington Post. “The reason things have moved so fast with [FA] trials is because of the community led by the people at [the Friedreich’s Ataxia Research Alliance] and those at Woodstock.”

Dr. Lynch, a pediatric neurologist and director of the Friedreich’s ataxia program at CHOP, attended FA Woodstock and used the opportunity to connect with families. He collected approximately 1,000 biosamples from those in attendance, both individuals with FA and their healthy family members, who volunteered to join a global registry to aid research on the disease.

Read more in the Washington Post story about FA Woodstock.

New Clotting Factor Shows Promise to Quickly Stop Uncontrolled Bleeding

CHOP researchers have developed a novel genetically engineered clotting factor that can control bleeding in animal models. If the factor proves effective in humans, it may provide a quick-acting countermeasure for surgery patients and others vulnerable to serious bleeding as a result of new blood-thinning drugs.

“This molecule holds the potential to fill an important unmet clinical need,” said study leader Rodney A. Camire, PhD, a hematology researcher in the Raymond G. Perelman Center for Cellular and Molecular Therapeutics at CHOP. “There are limited treatment options to stop uncontrolled bleeding in patients who are using the newer anticoagulant medications.”

Dr. Camire and colleagues from CHOP and the Perelman School of Medicine at the University of Pennsylvania developed the molecule by modifying coagulation FXa, a naturally occurring protein active in blood clotting. Using bioengineering techniques, the researchers altered the shape of FXa into a novel variant that is more potent, longer-lasting and safer than wild-type (naturally occurring) FXa.

They reported this week in Nature Medicine that the variant safely restored blood-clotting ability in injured mice that had previously received FXa inhibitors. Infusing the variant either before or during an active bleed significantly reduced bleeding.

Genetic Mutation Identified for a Craniofacial and Developmental Disorder

“This genetic syndrome represents a novel class of disorders,” said Kosuke Izumi, MD, PhD, a clinical geneticist and genetics researcher at CHOP.

Dr. Izumi led a team with colleagues from Japan, France, Belgium, and Singapore, that discovered the mutation responsible for a rare, newly identified genetic disorder that causes craniofacial abnormalities and developmental delays, reported this week in the American Journal of Human Genetics. The mutation disrupts normal protein transport within cells, shedding light on a fundamental process in cell biology and early human development.

Sequencing the genes of four unrelated individuals with similar clinical symptoms, the study team identified a mutation in a gene that encodes proteins in the COPI system, one of three systems that govern the transport of proteins between two structures within cells. The new syndrome is only the second known disease associated with the COPI protein complex.

The impairments in this transport process can cause stress-induced cell death or problems with collagen secretion, affecting bone and cartilage. The four patients’ intellectual disability also suggests a role for this genetic mutation in brain development.

Knowing the cause for their children’s symptoms has brought relief to the four families, Dr. Izumi noted, even though much more work remains to be done to better understand the disease mechanism and to discover therapies.

Dr. Izumi played a key role in a similar discovery of the multisystem disorder CHOPS syndrome, which helped bring three unrelated families together through their shared experience.

New Guidelines to Improve Detection of Abuse in Infants and Toddlers

Identifying when a child has been a victim of physical abuse is a critically important role that pediatric medical providers can play when they treat an injured child. But researchers have found racial and economic disparities in the level of screening injured toddlers receive for suspected cases of abusive head trauma (AHT). AHT is the leading cause of death among young victims of child maltreatment.

“Prompt recognition and accurate diagnosis of AHT is vital to providing appropriate medical treatment and protecting victims from further abusive injuries,” write Christine Payne, MPH, a clinical research coordinator, and Joanne Wood, MD, MSHP, a faculty member in CHOP’s PolicyLab, on the PolicyLab blog.

In an effort to develop standards to improve care quality and reduce disparities in care for these vulnerable young patients, Payne, Dr. Wood, and colleagues combined evidence from the medical literature with clinical perspectives of diverse physicians. They have now issued new guidelines which recommend near universal skeletal survey screening in infants less than 1 year of age with any intracranial hemorrhage.

“The recommendations for skeletal survey in children 1 to 2 years old, however, are much more dependent on the type of injury and history of trauma, reflecting the decreased risk for AHT in this population due to their increased mobility and risk for accidental head injury,” the authors write.

Read more on the PolicyLab blog.


In case you missed it earlier this week on Cornerstone, we brought you a conversation with Anne Ersig, PhD, RN, a new member of the Center for Pediatric Nursing Research and Evidence-Based Practice, about the role of nurses in pediatric research.

Last week’s In the News post covered a new accolade for a public health data-sharing tool developed by CHOP bioinformaticians, new research on the importance of vision outcomes after concussion, and a global meeting focused on the clinical and research issues facing a not-as-rare-as-you’d-think chromosomal disorder (22q11.2 deletion syndrome).

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