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Genetic Superheroes, Excess Bone, and Secondhand Smoke

Published on April 15, 2016 in Cornerstone Blog · Last updated 4 months 4 weeks ago


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Welcome back to another weekly roundup of research news from The Children’s Hospital of Philadelphia!

This week’s stories have elements that sound like fiction, but all are real, new scientific and medical findings: A condition that turns the body’s soft tissues into bone has new hope for a future treatment. Genetic superheroes walk among us, and they may not even know it. And pediatricians may have a tool to double their success in helping their patients’ parents quit smoking. Read on for the details.

Hope for Ending Excess Bone Growth

Researchers from CHOP and the University of Pennsylvania announced promising results with a drug candidate to stop crippling excess bone and cartilage growth in a mouse model of a rare disease.

Starting in early childhood, people with fibrodysplasia ossificans progressiva (FOP) begin to accumulate excess cartilage and bone growth in muscles and other tissues where it does not belong. This pathological process, collectively called heterotopic ossification (HO), causes progressive loss of skeletal motion and hampers breathing and swallowing.

"This work represents a big step toward therapy," said Maurizio Pacifici, PhD, a developmental biologist and director of Orthopedic Research in the Division of Orthopedic Surgery at CHOP, who was co-leader of the study published in the Journal of Bone and Mineral Research. "The mice used in this study were engineered to carry the human mutation that causes FOP, and the drug showed powerful and comprehensive benefits for skeletal growth and function in addition to inhibiting HO. If these results translate to humans, we may be able to treat children with FOP early in life, before the disease progresses."

An additional unexpected and exciting finding was that the drug, palovarotene, appeared better tolerated in mutant mice than in control mice. If this finding translates to patients, then the drug might be safer for children than anticipated.

Palovarotene was previously tested in adults with emphysema and had few side effects, but its testing was not continued beyond Phase 2 trials for that indication. Clementia Pharmaceuticals is currently conducting phase 2 clinical trials in individuals with FOP, based on 2011 preclinical results published by members of this study team. The FOP Center at Penn Medicine is one of four international sites for this trial, which is testing whether palovarotene is safe and effective in children and adults experiencing disease flare-ups.

Additional CHOP co-authors on the new study were study co-leader Masahiro Iwamoto, DDS, PhD, and Kenta Uchibe. Collaborators from Penn included FOP experts Eileen M. Shore, PhD (a study co-leader) and Frederick S. Kaplan, MD.

Read more in the CHOP press release.

Hidden Genetic Superheroes

Often, scientists studying the genetics of rare childhood diseases begin with a child who has clinical symptoms and then seek out the underlying genetic cause. A new study published this week in Nature Biotechnology took the opposite tack: Scientists mined genetic data from more than 500,000 participants in several large biobanks, including CHOP’s biobank in the Center for Applied Genomics, looking for participants whose genes had rare mutations that were thought to universally cause severe and debilitating childhood conditions — and then narrowed the field down in search of individuals whose medical records indicate they reached adulthood without ever having developing those conditions.

Such individuals may have become resilient because they harbor additional, protective genetic mutations that scientists have yet to identify. If found, these protective mutations could point the way to therapies for individuals with only the harmful mutations.

The researchers found a total of 13 people who seem to meet these criteria of “genetic superheroes.” But these 13 people are likely unaware of their status. None of these individuals signed consent forms that permitted researchers to re-contact them after their initial participation in other studies. As we reported in Bench to Bedside this month, many of the participants in CHOP’s genomics biobank did sign an innovative consent form that allows researchers to re-contact them in the future. None of the 13 suspected “genetic superheroes” found in this study was in the CHOP biobank.

The study was led by investigators at the Icahn School of Medicine at Mount Sinai in New York, with co-authors from CHOP including Lifeng Tian; Patrick Sleiman, PhD; Matthew Deardorff, MD, PhD; Elaine Zackai, MD; and Hakon Hakonarson, MD, PhD.

Read more in the in Nature Biotechnology paper, and in Wired and The Atlantic.

Pediatricians Can Help Parents Quit Smoking

More than 40 percent of U.S. children are exposed to secondhand smoke, which contributes to numerous health risks. But quitting smoking isn’t easy for parents even when they know they should.

“Pediatricians are uniquely positioned to educate and motivate parents to protect their children from secondhand smoke,” wrote Brian Jenssen, MD, a primary care pediatrician at CHOP in a PolicyLab blog post. “Although interventions through pediatric settings are effective in helping parents quit, various system-level barriers have limited adoption and sustainability. Both nationally and in Pennsylvania, very few parents who smoke and accompany their child to the pediatrician’s office are offered treatment or given advice to help them quit.”

Dr. Jenssen, a Robert Wood Johnson Clinical Scholar at Penn, was lead author of a study published online this week in Pediatrics showing that simple reminder tools embedded in electronic health records can empower pediatricians to help parents quit using tobacco. Their intervention more than doubled rates of smoking cessation counseling. Based on these results, the team plans to expand their study of the tool they developed, including evaluation of its use in more clinics and collecting data on parents’ actual quitting rates.

Co-authors from CHOP were Tyra Bryant-Stephens, MD; Robert Grundmeier, MD; and senior author Alexander Fiks, MD, MSCE.

Read more on the CHOP PolicyLab blog.


In case you missed it, this week on Cornerstone we brought you a Q&A about teen dating violence research, a subject that is emerging as its own field of study distinct from research on intimate partner violence in adults.

Last week’s “In the News” summary shared another Pediatrics article with Dr. Fiks as senior author, reporting patterns of diagnosis for mental health conditions; announced that a CHOP oncology leader is joining the Blue Ribbon panel to advise the Vice President’s cancer moonshot initiative; and reported the CHOP-led discovery of a genetic syndrome that causes intellectual disability.

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