Welcome back to another weekly roundup of research from The Children’s Hospital of Philadelphia! This week’s stories span discovery (of a potential treatment for rare blood diseases), inspiration (from a mother who transformed grief over her daughter’s terminal disease into a foundation helping other families), and finding practical clinical insight (to distinguish a serious knee condition from a drug-treatable infection with similar symptoms). Read on for the details.
Potential Treatment for Blood Diseases is a Double Whammy
A compound that regulates iron in the blood could potentially treat two serious genetic blood diseases affecting children and adults, according to new research by a CHOP team published online last week in the journal Blood.
“It seems counterintuitive that one compound could treat two diseases that are quite different, but by restricting iron absorption, it also helps to normalize red blood cell levels in animals,” said study leader Stefano Rivella, PhD, a hematology researcher at CHOP and professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. “If these preclinical results translate to humans, this could represent a new treatment for both disorders.”
Working with colleagues including first author Carla Casu, PhD, Dr. Rivella tested minihepcidins in mouse models of the diseases beta-thalassemia and polycythemia vera (PV). Minihepcidins are modified versions of the naturally occurring hormone hepcidin that regulates iron. They are smaller than the full-length hormone but have long-term stability and long-lasting biological activity when administered to animals.
In their animal models of both diseases, the researchers found that minihepcidin normalized levels of red blood cells (RBCs). Beta-thalassemia is characterized by too few RBCs, because patients have a genetic disorder of impaired hemoglobin production that results in both impaired ability to carry oxygen in RBCs, and a vicious cycle that causes destruction of these RBCs as well. In PV, rare mutations drive the overproduction of RBCs, gradually thickening the blood into a ketchup-like consistency and raising the risk of high blood pressure and thrombosis (clotting), which may cause a stroke.
A Mother’s Perspective
On Mother’s Day this past Sunday, our thoughts turned to the remarkable mothers of children with serious childhood diseases that pediatric researchers are devoted to understanding, treating, and curing. One mother in particular shared an especially inspiring story in an essay in Slate.
“My daughter has taught me that when the worst possible thing happens, you have nothing left to fear,” wrote Maria Kefalas, mother of 6-year-old Calliope (Cal). “She has taught me that fearless people are maddening and relentless, and if we are fortunate, we can find a way to honor our children by changing the world. She has taught me that when you have tamed your fear, you harness its power to do extraordinary things. In the end, the only way to save yourself from the grief is to find a way to help other families.”
Kefalas and her family started selling cupcakes for $1 each, raising awareness and funds to help children with leukodystrophy, the neurodegenerative disease affecting Cal. A new experimental gene therapy for Cal’s form of the disease is in trials in Europe, but although she knew the trial couldn’t help Cal because her terminal condition was already too advanced, Kefalas and her Calliope Joy Foundation used the funds they raised to help other families access the experimental therapy.
“Because of the cupcakes, we are now working with researchers and doctors to get this revolutionary new therapy to the United States as quickly as possible,” Kefalas wrote. “Cal’s neurologist, Dr. [Amy] Waldman, now leads a Leukodystrophy Center at the Children’s Hospital of Philadelphia. There, leukodystrophy is no longer an orphan disease — instead it is a major initiative, with 35 specialists and researchers championing these children.”
Distinguishing a Serious Knee Problem from Lyme Disease
Knee pain and swelling can be among the symptoms of Lyme disease, a tick-borne bacterial infection that is treated with antibiotics. But these symptoms can also indicate septic or infectious arthritis of the knee, a medical emergency requiring surgical intervention to prevent irreversible knee damage. And both conditions can have similar co-occurring symptoms, including fever and swelling of other joints.
Seeking better ways to distinguish the two conditions in children and ensure patients receive appropriate and timely treatment, researchers reviewed the records of 189 patients under age 18 who presented at CHOP with excess fluid in the knee between 2005 and 2013. They identified four factors that are predictive of septic arthritis.
"The probability of septic arthritis with any one factor present was 18 percent compared to 100 percent will all four factors present," said study author Wudbhav N. Sankar, MD, an orthopedic surgeon at CHOP. "Our study offers a useful prediction algorithm to help distinguish septic arthritis from a knee effusion caused by Lyme disease in children."
Read more in the press release from the American Academy of Orthopaedic Surgeons and the study published in the Journal of Bone and Joint Surgery.
In case you missed it, this week on Cornerstone we shared an innovative perspective that is shaping CHOP’s approach to antimicrobial stewardship: socio-behavioral research.
And don’t forget to check out the April issue of Bench to Bedside, which includes new applications of computer science for photo analysis in dermatology, an investigation into the mechanisms of brain injury in concussion, and more.
Last week’s “In the News” summary featured CHOP joining the nation’s largest genetic study of autism spectrum disorder, youth violence research getting attention in the state’s capital, and an important perspective on helping babies born dependent on opioid drugs.
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