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In The News: ADHD, Humanized CAR T-Cell, Obesity, Malaria, Fetal Surgery

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July 9, 2021
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limjr [at] chop.edu (By Jillian Rose Lim)

From malaria and mosquitoes to mitigating mental health concerns, this week's roundup of research news highlights the many ways scientists are safeguarding children's health through scientific inquiry. Learn about a potential link between attention-deficit/hyperactivity disorder (ADHD) medications and reduced suicide risk, discover how a malaria parasite survives temperature shifts, read about the development of humanized CAR T-cell therapy, and more.

ADHD Medications May Reduce Suicide Risk in Children With Behavioral Symptoms

Amid steadily rising suicide rates in children, new research leveraging data from nearly 12,000 U.S. children suggests that ADHD medications may reduce the risk of suicide in those with hyperactivity, oppositional defiance, and other behavioral disorders. Researchers in the Lifespan Brain Institute (LiBI), a collaboration between CHOP and the University of Pennsylvania, published the findings in JAMA Network Open.

"Early diagnosis and treatment of behavioral symptoms with ADHD medication, particularly among children with severe externalizing symptoms, may serve not only to improve learning and behavior problems, but also to decrease suicidality risk," said Ran Barzilay, MD, PhD, the study's senior author and an assistant professor at LiBI, in a press release. "These symptoms are treatable, and addressing them early has the strong potential to prevent and mitigate serious mental health issues later in life."

Dr. Barzilay and his team worked with researchers at Tel Aviv University to analyze data from the Adolescent Brain Cognitive Development (ABCD) Study, the largest long-term study of brain development and health in the U.S. Out of the 11, 878 children in the study, 8.5 percent were treated with ADHD medication and 8.8 percent reported past or current suicidality. The researchers found that among those children who demonstrated significant externalizing behaviors, those taking ADHD medication had lesser odds for suicidality. One year later, those children were less likely to be suicidal, while those not receiving ADHD medications at baseline (but had high externalizing symptoms) were more likely to be suicidal.

Learn more in the press release.

Humanized CAR T-Cell Therapy Shows Potential for Relapsed B-ALL

Chimeric antigen receptor (CAR) T-cell therapy, wherein a patient's T-cells are engineered to find and fight cancer cells, has transformed how clinicians treat B-cell acute lymphoblastic leukemia (B-ALL), a disease once considered incurable. Still, as many as 50 percent of patients who receive the treatment eventually relapse, due in part to the potential loss of CAR T-cell persistence. Researchers hypothesize that a patient's body might reject the treatment because of the "non-human" domain in CARs derived from mouse monoclonal antibodies. Now, new findings show that a humanized CAR T-cell therapy developed by CHOP researchers proved to be a safe approach with high response rates and lasting remissions in children and young adults with relapsed or refractory B-ALL.

The researchers developed the CAR containing a "humanized" anti-CD19 domain (huCART19) to look as if it had been derived from a human cell line rather than a mouse model. When the team assessed the treatment in 74 children and young adults with relapsed B-ALL, they found it to be effective – particularly so in patients who had not previously received CAR T-cell therapy treatment. One hundred percent of those patients experienced complete remissions. One year later, the probability of remaining disease-free was 84 percent; two years later, it was 74 percent.

"These results show that humanized CART19 is an encouraging option for retreatment in a difficult-to-treat population," said Shannon L. Maude, MD, PhD, senior author of the study and an attending physician in the Center for Childhood Cancer Research at CHOP. "We are continuing to analyze the effectiveness of this approach in a phase 2 trial, which is ongoing."

Learn more.

How Has the COVID-19 Pandemic Affected Childhood Obesity?

Recent research from PolicyLab found that the average obesity prevalence in a cohort of children increased almost 2 percent during the COVID-19 pandemic – a finding potentially due to the disruption of physical education, activity, and family routines while sheltering at home.

Brian Jenssen, MD, MSHP, and his colleagues took a close look at obesity rates for patients visiting the CHOP Care Network. They measured the patients' body mass indexes (BMI) monthly from January 2019 to December 2020 and compared them to obesity rates prior to the pandemic. The researchers found that average obesity prevalence increased from 13.7 percent to 15.4 percent, with a particularly pronounced increase among patients ages 5 to 9 years and Hispanic, non-Hispanic Black, publicly insured. and lower-income youth. The findings also suggest that during the pandemic, preexisting disparities in obesity significantly widened.

"While a 2 percent increase may seem small, this translates to an additional 6,000 children in our Care Network, or an additional 1.5 million children nationally, who are now obese," wrote Dr. Jenssen in a PolicyLab summary of the work. "Entering pandemic recovery, there are steps we can take to address these trends. Pediatricians can work with caregivers to recommend strategies tailored to families, such as virtual activities that promote physical activity, or connect them to nutritious meals offered through community settings. As we look ahead, it will also be essential to ensure children can safely return to school where they have more opportunities to engage in physical education, have access to healthy meals, and more."

Learn more on PolicyLab's website.

Researchers Elucidate How Malaria Parasites Survive Temperature Shifts

Disabling a malaria parasite's ability to survive dramatic shifts in temperature – a skill that allows it to wreak havoc on the human body – could help scientists develop new and effective antimalarial drugs. In a new paper published in mBio, Audrey Odom John, MD, PhD, Chief of the Division of Pediatric Infectious Diseases, and her team described how the cold-blooded creature finds itself living in a much warmer temperature (about 98.6 degrees Fahrenheit) once inside the human body, and then at an even higher temperature (up to 106 degrees Fahrenheit) when that human's fever spikes.

Dr. John and her colleagues identified a heat-shock protein in the parasite that helps it to survive temperature changes but only with the addition of a particular lipid through a process called prenylation. Without prenylation, the protein cannot function properly, leaving the parasite susceptible to temperature shifts.

"The rise of antimalarial resistance threatens malaria control efforts worldwide, which is why there is a huge need for new antimalarial drugs," said Dr. John, who is senior author of the paper. "Several drugs in development already target this prenylation process and kill malaria parasites in the test tube. Our study suggests that these new treatments may be even more effective when given to people with malarial fevers."

Learn more.

Philadelphia County Medical Society Honors N. Scott Adzick, MD

Join us in congratulating N. Scott Adzick, MD, Surgeon-in-Chief at CHOP and a pioneer in the field of fetal surgery, for his receipt of the Strittmatter Award, the most prestigious scientific honor of the Philadelphia County Medical Society (PCMS). The award recognizes a PCMS physician who has demonstrated the most valuable contributions, whether surgical or medical, to the practice of healing.

"I am honored to receive this award from the Philadelphia County Medical Society, recognizing work that has helped so many patients and families," said Dr. Adzick in a press release. "At CHOP, we hope that continued research in the field of fetal surgery will bring better treatments to even more patients, both here in Philadelphia and around the world."

In 1995, Dr. Adzick founded the Richard D. Wood Jr. Center for Fetal Diagnosis and Treatment, the largest and most comprehensive fetal program in the world. Over the last four decades, Dr. Adzick and his colleagues have performed more than 2,000 fetal surgeries and cared for more than 25,000 expectant mothers, making the innovative procedure a widespread and life-changing option for babies and families. Dr. Adzick remains at the forefront of refining fetal surgery research, leading studies that show fetal surgery can significantly improve outcomes for children with spina bifida, leading to better quality of life.

Learn more in the CHOP press release.

ICYMI

Catch up on our headlines from our June 25 In the News:

  • Milestone Reached: CHOP Celebrates Birth of 2,000th Fetal Surgery Patient
  • And the Newly Elected Presidents are...
  • Colin Conine, PhD, Named 2021 Pew Scholar in Biomedical Sciences
  • Welcome, Injury Science Research Experiences for Undergraduates Class of 2021

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