Category: Science

New Brain Study Tailored for Nonverbal Children on the Autism Spectrum

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Originally published in Bench to Bedside, the CHOP Research monthly publication.

I composed this original article based on interviews with the investigators.

Excerpt:

The children who speak least — or not at all — are rarely represented in cutting-edge brain imaging research on autism spectrum disorder (ASD). Researchers at The Children’s Hospital of Philadelphia aim to change that with a new study enrolling children with ASD who are minimally verbal or nonverbal.

“This is really an underserved community who have not been given the opportunity to participate in research,” said Timothy Roberts, PhD, vice chair of research in the Department of Radiology at CHOP and a professor of Radiology at the Perelman School of Medicine at the University of Pennsylvania. “More importantly, the results of the research are not directly applicable to them, so even if we developed a drug for ASD impairments led by our biomarkers, we wouldn’t know if this treatment really was good for individuals with ASD with more limited verbal and cognitive ability.”

Dr. Roberts and colleagues from CHOP’s Center for Autism Research want to know whether certain aspects of neural rhythms and timing of neural firing that they found to be characteristic of ASD in previous studies, using noninvasive brain imaging called magnetoencephalography (MEG), are indeed common across the spectrum.

“When neural activity is happening, it produces electrical and magnetic fields,” said J. Christopher Edgar, PhD, a co-leader of the study and a clinical neuropsychologist and brain imaging researcher in the Department of Radiology at CHOP. “We use this machine to measure the magnetic field. We do that to look at brain function.”

The neural biomarkers that Dr. Edgar and Dr. Roberts have found correlate with the level of clinical impairment in the children they have studied to date, particularly in the realm of language ability.

“There is a scientific question: Does this correlation extend into this nonverbal and minimally verbal population in a continuous way, or is it a separate disorder?” Dr. Roberts said. “I suppose a fundamental question is: Is the autism spectrum continuous or discrete in terms of these brain markers?”

Researchers Test Magnetic Re-Seeding to Speed Blood Vessel Recovery

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Originally published in Bench to Bedside, the CHOP Research monthly publication.

I composed this original article based on an interview with the investigator.

Excerpt:

Reopening blocked blood vessels can mean the difference between life and death for many patients, including children with pulmonary hypertension and adults with coronary artery disease. But the procedure used for restoring blood flow can cause extensive vascular injury, wiping away an essential protective layer of cells lining the walls of arteries and veins: the endothelium.

It may take the body weeks or months to heal that damage. Some long stretches of damaged vessels may never fully regrow the endothelium, which naturally propagates inward from the healthy edge toward the center of the wiped-out area.

“Our idea is that if we could put some seeds of endothelium regrowth within the boundaries of this denuded arterial segment, so that the endothelium can grow from those foci, we could speed up the process dramatically,” said Michael Chorny, PhD, a researcher at The Children’s Hospital of Philadelphia and research assistant professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, who specializes in developing delivery systems for therapies. “By changing the pattern of endothelium recovery, we may in practice restore it on scale of days.”

Early Smell Exposure May Be Critical for Sensory Development

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Originally published in Bench to Bedside, the CHOP Research monthly publication.

I composed this original article based on interviews with the investigators.

Excerpt:

Many parents try to offer their healthy babies a rich sensory environment, full of new sights, sounds, smells, and tastes, to stimulate the developing brain to appreciate life’s delicious complexities to the fullest. And for vision and hearing, there is a solid foundation of research showing that there is a critical period early in life when adequate stimulation of those senses is essential for their healthy development.

Now, a pilot study conducted at The Children’s Hospital of Philadelphia and published in the journal JAMA Otolaryngology provides some of the first-ever evidence for a critical period in developing the sense of smell, or olfaction, too. The findings have particular implications for rehabilitating young patients, including severely premature infants, who receive lifesaving medical interventions that temporarily prevent airflow through the nasal passages during this potentially critical period.

Four Projects, One Goal: Curing Childhood Cancer

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Originally published in Bench to Bedside, the CHOP Research monthly publication.

I prepared this article based on the project descriptions and email correspondence with the investigators.

Excerpt:

Many cancer treatments have harmful side effects when they act on healthy tissues in addition to cancer cells. A team led by Garrett M. Brodeur, MD, director of the Cancer Predisposition Program at CHOP, and funded by a CURE grant, is seeking ways to increase drug delivery to the tumors to improve drugs’ effectiveness while reducing their toxicity.

Their method uses tiny nanoparticles as delivery vehicles. Nanoparticles are a promising way to get drugs into tumors because tumor blood vessels are leaky, and the nanoparticles can enter the tumor much more easily than normal tissues.

“By increasing drug delivery to tumors by one or two orders of magnitude, we can achieve dramatically better anti-tumor effects while simultaneously decreasing total drug exposure to patients,” Dr. Brodeur said.

New CHOP Investigator Combines Bioinformatics and Cancer Genomics

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this profile based on an interview with the investigator.

Excerpt:

“I’m excited being here at the right time,” said Kai Tan, PhD. “Hopefully we can really push translational medicine in cancer, faster, with our new algorithms.”

It is the “right time” because Dr. Tan, a cancer genomics and bioinformatics researcher, joined The Children’s Hospital of Philadelphia in January. Within weeks of his arrival, Vice President Joe Biden launched the cancer “moonshot” initiative during a visit with cancer researchers from the University of Pennsylvania and CHOP at Penn’s Abramson Cancer Center.

The rapid expansion of precision medicine in cancer — in which researchers aim to develop clinical treatments precisely targeted to a tumor’s genetic profile — has created an urgent need for scientists like Dr. Tan, who has pioneered the development of novel computational strategies and systems biology to identify molecular events that drive cancers.

Proton Therapy Neuropsychology Study Receives Dissertation Award

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Originally published on Cornerstone, the CHOP Research Blog.

I composed this original article based on interviews with the investigators.

Excerpt:

Babies being treated for brain cancer have not received traditional radiation therapy since the 1980s. At that time, doctors realized that the side effects of radiation hitting healthy developing brain tissues in very young children was simply too severe. But within the past decade, proton therapy has become available to some of even these youngest patients. This newer radiation therapy method has a more targeted radiation beam that better concentrates its effect on the tumor while hitting fewer healthy tissues — but the nature of its effects on the developing brain are still being studied.

One such study, a doctoral dissertation project by a researcher at The Children’s Hospital of Philadelphia, was recently recognized for its quality of design and potential impact with the John E. Gordon Dissertation Award from the Philadelphia Neuropsychology Society (PNS) and Clinical Neuropsychology Associates.

Beyond Imagining: Pediatric HIV Research Faces the Future

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Originally published in the 2015 CHOP Research Annual Report.

I composed this original article based on multiple interviews and background literature research.

Excerpt:

The HIV epidemic in 2015 and beyond is a dramatically different one than ever seen or imagined during the height of the AIDS crisis in the 1980s and ‘90s.

“In the early days, up to a quarter of all infants born to women with HIV became infected. Now it’s less than one percent,” said Richard Rutstein, MD, an HIV clinical research leader and medical director of the Special Immunology Service at The Children’s Hospital of Philadelphia since its inception in 1989. “For those infected, HIV has changed from a rapidly fatal disease to a chronic illness.” Dr. Rutstein is also a professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.

At the front line of this evolution, CHOP researchers are helping infected pregnant women, infants, children, and youth around the world live full, productive lives.

Scientists Discover a Better ALK Inhibitor to Treat Neuroblastoma

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Originally published on Cornerstone, the CHOP Research Blog.

I edited this article based on a CHOP press release and an additional interview with the investigator.

Excerpt:

Pediatric cancer researchers at The Children’s Hospital of Philadelphia believe they have succeeded in their search for a powerful next-generation drug for neuroblastoma tumors with mutations in the anaplastic lymphoma kinase (ALK) gene associated with the cancer. Based on their preclinical findings, they are fast-tracking the launch of a clinical trial this year.

Usually appearing as a solid tumor in the chest or abdomen, neuroblastoma accounts for a disproportionate share of cancer deaths in children, despite many recent improvements in therapy.

The search for better ALK inhibitors originated when, in 2008, CHOP pediatric oncologist Yael Mossé, MD, and colleagues identified ALK mutations as a driver of most cases of rare, inherited neuroblastoma. Subsequent research showed that abnormal ALK changes drive approximately 14 percent of high-risk forms of neuroblastoma.

Based on this knowledge, scientists including Dr. Mossé in the multicenter Children’s Oncology Group were able to repurpose crizotinib, an ALK inhibitor already approved to treat adults with lung cancer, in clinical trials of children with neuroblastoma. But they found that different mutations within the ALK gene in neuroblastoma responded differently to crizotinib, and a mutation labelled F1174L was resistant to the drug.

How Precision Medicine is Reshaping Epilepsy Research

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on multiple interviews with the investigators.

Excerpt:

The little girl’s epilepsy was so debilitating that she was virtually nonresponsive. Traditional antiseizure medicines could not reduce the five to 20 seizures she experienced daily when she first came to The Children’s Hospital of Philadelphia.

Trying a new approach, her neurologist, David Bearden, MD, prescribed a drug that targeted a molecular pathway involved in her seizures, and within a month, she was seizure-free for the first time since a few days after her birth.

This success excited hope among epilepsy researchers worldwide that other such successful strategies could soon follow. The case exemplifies the popular concept of precision medicine, which is barreling ahead in cancer but not yet common practice in neurologic disorders such as epilepsy.

“Most drugs for epilepsy work like treating pneumonia with a cough suppressant: It may stop the symptom but doesn’t treat the underlying problem,” said Ethan Goldberg, MD, PhD, a CHOP neurologist and neuroscientist who was senior author of a case report about the little girl’s treatment (of which Dr. Bearden was first author) in Annals of Neurology in 2014. Her treatment, while not yet analogous to an antibiotic, was more precisely targeted to the underlying mechanism of her seizures than most treatments.

The future need for precision medicine is one that epilepsy researchers are approaching with conscious attention to the field’s strengths and unmet challenges. Dr. Goldberg was a presenter at a precision medicine scientific symposium during the American Epilepsy Society annual meeting in December. His colleague, Dennis Dlugos, MD, MSCE, a CHOP pediatric neurologist, was among the major contributors to an international consortium of researchers who authored a roadmap for precision medicine in epilepsy published in The Lancet Neurology this fall.

New Collaboration Uncovering a Mitochondrial Mystery

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Originally published in Bench to Bedside, the CHOP Research monthly publication

I composed this original article based on an interview with the investigator.

Excerpt:

Mistakes happen. Inside every cell, the functions of life rely on the basic process of building proteins. But, about half the time, cells make errors when building proteins and have to recycle the pieces and start again. One important player in the cell’s recycling process, an enzyme called N-glycanase 1 (NGLY1), is at the center of a new, fundamental biological mystery that researchers at The Children’s Hospital of Philadelphia are setting out to solve.

Two young patients brought this mystery to the team’s attention. Both children arrived within a short time of each other with symptoms of suspected mitochondrial disease at CHOP’s Mitochondrial-Genetic Disease Clinic, which Marni Falk, MD, directs. Mitochondria are the organelles inside of cells that act as the cell’s energy generator, and diseases of mitochondria can have wide-ranging effects across every organ system and commonly include neurological and cardiac complications.

“There are a lot of areas of mitochondrial biology that are still not known at all,” said Dr. Falk, an attending physician at CHOP. “We’ve been so intrigued with this project because, every time we asked a question, three more questions followed.”

Dr. Falk and her team found that, instead of a primary mitochondrial disease, these two children had an extremely rare genetic disorder that was only recently identified, caused by an inherited deficiency in the protein-recycling enzyme, NGLY1. This was fundamentally weird. There was no evident logical reason for a disease of NGLY1 dysfunction to so closely resemble diseases of mitochondrial dysfunction because the proteins in mitochondria do not require NGLY1’s services, or so says conventional wisdom.