Mar 26 2014

CHOP Pediatric Psychology Experts to Shine at SPPAC

Pediatric psychologyPediatric psychology is embedded into family-centered care at The Children’s Hospital of Philadelphia. When a child has a serious or chronic illness, pediatric psychologists listen carefully and empathetically to concerns of the young patient and family while assessing their strengths, coping strategies, and goals. Pediatric psychologists also work to improve the welfare of well children in healthcare settings, and they conduct a variety of research activities, such as finding ways to increase adherence to medical treatments.

Several of CHOP’s experts in this multidisciplinary field will be sharing their insights at the Society of Pediatric Psychology Annual Conference (SPPAC) being held in Philadelphia March 27-29.

The SPPAC will introduce a fresh format for the meeting, which will attract pediatric psychologists, researchers, and other specialists who have training and experience in addressing the emotional, cognitive, and developmental needs of medically fragile children. SPPAC Chairperson Lisa Schwartz, PhD, a psychologist in CHOP’s division of oncology, has organized many of the new elements that will be integrated into the 2014 conference.

“It’s been exciting to help shape the conference and be a firsthand witness to all the innovation in the field,” said Dr. Schwartz, who will officially welcome SPPAC attendees during opening remarks March 28.

A “first” for the conference is the incorporation of a theme, “Pediatric Psychology: From Infancy to Adulthood.” Presentations will reflect a lifespan and developmental perspective that focuses on findings from early childhood to young adulthood. They also will promote the maturation of the science of pediatric psychology via technology, advanced statistical or research designs, translational science, and team science.

The conference will offer more workshops and concurrent symposia than ever before along with research blitz sessions that will cover novel and noteworthy advances, Dr. Schwartz said. Fifteen special interest group meetings will facilitate collaboration.

Dr. Schwartz is eager to hear the keynote presentation, “An Integrated Framework for Linking Exposure and Phenotypic Data in the National Children’s Study,” by Captain Steven Hirschfeld, MD, PhD, director of the National Children’s Health Study. By following 100,000 children from before birth to age 21, study researchers hope to better understand how children’s genes and their environments interact to affect their health and development. The Children’s Hospital of Philadelphia is a site of this important study.

CHOP psychologists will present talks throughout the conference, including one that Dr. Schwartz will give March 28 on young adults’ transition to adult medical care. Dr. Schwartz highlighted a few other “not-to-miss” examples of CHOP’s contribution:

Jodi Mindell, PhD, associate director of the Sleep Center at CHOP, will be a speaker at one of the six pre-conference workshops March 27. During “Pediatric Behavioral Sleep Medicine: Tips and Tools for Practitioners,” attendees will learn about intervention strategies for a variety of sleep difficulties in pediatric patients, including insomnia, circadian rhythm disturbances, childhood fears, and non-adherence to positive airway pressure therapy.

Paul Robins, PhD, program director of pediatric psychology at CHOP, will participate March 28 in a panel discussion, “The Maturation of Pediatric Psychology Training: 2013 Society of Pediatric Psychology Task Force Recommendations.” He also is part of a symposium March 29 and will speak about, “Translating Competencies Into Practice: Internship Training in Clinical Child Psychology.”

Meghan Marsac, PhD, a CHOP clinical psychologist and behavioral researcher, is chairing a symposium, “Utilizing Web-based Programs to Promote Child Health,” March 29. She also will give a talk on the application of an internet-based game for secondary prevention of post-traumatic stress following acute medical events. Nancy Kassam-Adams, PhD, co-director of CHOP’s Center for Pediatric Traumatic Stress, will be the discussant.

SPPAC provides an ideal forum for networking and career building. Students, trainees, and early career professionals who pre-register for a mentoring lunch March 28 will have the opportunity to consult with more than 25 established investigators and clinicians from CHOP who can help them to navigate research careers in pediatric psychology.

The three-day conference will take place at the Loews Hotel in Center City Philadelphia, and it is expected to draw more than 500 researchers and practitioners from the Delaware Valley and beyond.

Permanent link to this article: http://www.research.chop.edu/blog/chop-pediatric-psychology-experts-shine-sppac/

Mar 24 2014

CHOP Researcher Advances Adolescent Care in Africa

adolescents

Dr. Lowenthal examining an African child in Botswana.

A Children’s Hospital of Philadelphia pediatrician’s research projects span across continents to Botswana, a sub-Saharan African country with a busy clinic for 2,000 HIV-infected children and adolescents who stole her heart.

Elizabeth Lowenthal, MD, MSCE, remembers noticing a remarkable 12-year-old boy in Botswana, “a real leader” who spontaneously sat down and began translating for an American social worker who had recently arrived to organize a camp for patients. Smart and engaging, he did well on antiretroviral therapy until he became an older teenager. He struggled with his adherence, ended up failing his treatment, and became resistant to the medications.

Dr. Lowenthal brought this lesson to CHOP, along with many others that she learned while living for four years in Botswana, where she provided care as the clinical director of the Botswana-Baylor Children’s Clinical Centre of Excellence. She began practicing there in 2004, when the country was just getting antiretroviral treatment. Currently, more than 3 million children worldwide are affected by HIV, and more than 90 percent live in sub-Saharan Africa.

“Lots and lots of people in Botswana are infected, and just about everybody is affected one way or another by HIV,” Dr. Lowenthal said. “Botswana has better resources than most of the countries in sub-Saharan Africa, so figuring out what can work there hopefully can translate to where most of the kids are.”

As one of the only pediatricians at the time treating children with HIV in Botswana, Dr. Lowenthal became involved with government committees that were creating public health policies for the country. The committee members would turn to Dr. Lowenthal for recommendations for the pediatric population with HIV, but she found that there were little data in the literature to guide some of their decisions.

So while her heart was still in Botswana, she returned to the U.S. and began a research fellowship at CHOP to learn how to scientifically approach these questions. Dr. Lowenthal is now an assistant professor of pediatrics at CHOP, a staff physician at the Special Immunology Family Care Center, and lead research physician for CHOP Global Health.

In her first major research publication in the Journal of the American Medical Association, Dr. Lowenthal’s findings supported the use of efavirenz as initial antiretroviral treatment because it was associated with less virological failure when compared to another drug, nevirapine, which is used more commonly in children. The study influenced not only the treatment guidelines in resource-limited settings, such as Botswana, but it also helped to clarify U.S. guidelines.

adolescentsMost of her current work is focused on adherence to HIV treatments among perinatally HIV-infected adolescents in Africa, a fast-growing population. Good treatment outcomes have allowed more children with HIV to reached young adulthood, and now they face unique challenges. As Dr. Lowenthal described in a recent Lancet Infectious Diseases review paper, they must confront psychosocial issues, negotiate decisions about sexual relationships, and manage a chronic illness during a period of rapid physical and psychological changes. Unfortunately, this tumultuous time threatens the longevity of their treatment.

“While these treatments are lifesaving and amazing, they only work if you take them consistently,” Dr. Lowenthal said. “If they miss doses for a period of time, they develop resistance to them. Many adolescents, unfortunately, are losing the limited treatment options that they have. If we can’t support adherence well enough, all of these other problems are not going to be relevant because kids aren’t going to continue to survive.”

Her research projects take many perspectives to help predict which adolescents are going to have difficulty with adhering to their medication long-term. Recognizing those children who would most likely benefit from support services could be an important first step to possibly preventing their failure, Dr. Lowenthal said.

An ongoing study is comparing methods that measure adherence to determine which are the most useful among HIV-infected adolescents in Botswana. These methods include self-report, electronic monitoring devices, pill counts, medication refill rate, and monitoring virus suppression. Dr. Lowenthal’s research team also is considering how adolescents’ autonomy over medication is associated with these measurement methods.

In a pilot study published in AIDS Care, her research team evaluated the Pediatric Symptom Checklist (PSC) as a simple screening tool to identify children and adolescents with psychosocial needs. A prospective study is under way to assess whether high scores on the PSC precede adherence problems and treatment failure. Once these psychosocial areas are identified, healthcare providers could use them as starting points for interventions.

“In a setting where you have thousands of kids, trying to figure out what are the big issues that we need to approach is really important,” Dr. Lowenthal said. “They are certainly complex problems that need complex solutions. We are starting with just trying to understand what’s at the root.”

adolescentsDr. Lowenthal’s work in Botswana has crossover to her clinical work in the Special Immunology Family Care Center, where she and her team provide treatment for about 150 HIV-infected children. For example, artists at CHOP adapted a book created for children in Botswana to help initiate discussions about their HIV status. In the version for the American children, the good guys are superheroes instead of soldiers, and the kids play basketball instead of soccer, but the message is the same: Taking your antiretroviral medications keeps your body strong.

Dr. Lowenthal keeps in touch with some of her patients in Botswana, and her research allows her to visit two or three times a year. The amazing young man she met during her early years in Africa is now in his twenties and doing better again. Yet, she continues to ask: “What could I have done to have kept him from losing options and struggling during his teenage years?”

A CDC-PEPFAR Public Health Effectiveness Grant funds Dr. Lowenthal’s work, and additional questions related to optimizing adherence measurement and defining developmental and psychosocial factors associated with nonadherence are funded by an NIH K23 Career Development award.

Permanent link to this article: http://www.research.chop.edu/blog/chop-researcher-advances-adolescent-care-africa/

Mar 21 2014

CHOP Sports Medicine, Concussion Specialist Interviewed by Fox 29

concussion

Christina L. Master, MD, was recently interviewed on Fox 29’s Good Day Philadelphia during a segment about sports injuries and concussion.

The Children’s Hospital of Philadelphia’s Christina L. Master, MD, was recently interviewed on Fox 29’s Good Day Philadelphia during a segment about sports injuries and concussion. In part a report about the recently released documentary film Head Games: The Global Concussion Crisis, Dr. Master discussed the appropriate age for children to begin playing contact sports and helmets, among other topics.

After being asked when it was safe for kids to being playing contact sports like hockey and football, Dr. Master said “we do think that contact sports ought to be held off until they’re older … probably into the middle school, the teenage years.”

Indeed, citing USA Hockey’s example, Dr. Master noted experts urge younger children to focus on fundamental skills, and not participate in contact skills like checking in hockey or heading soccer balls. As part of its Progressive Checking Skill Development Program, USA Hockey recommends that legal body checking not begin until age 13 or 14.

When asked if improved helmets might reduce concussions, Dr. Master pointed out that “when you think about the fact that a concussion is your brain shaking in your skull, there’s really no way a helmet with protect 100 percent against that.”

And when asked what advice Dr. Master might have for parents, she said, “I think it’s important to, as a parent, choose a situation that’s conducive to learning fundamental skills … the idea is to learn the skills, have fun, be fit,” she added.

For more, see the full interview below!

Philadelphia News, Weather and Sports from WTXF FOX 29

Permanent link to this article: http://www.research.chop.edu/blog/chop-sports-medicine-concussion-specialist-interviewed-fox-29/

Mar 19 2014

U.S. News Ranks Department of Pediatrics No. 1 in Nation

pediatricsEach year, U.S.News & World Report ranks professional school programs in business, education, engineering, law and medicine. In its latest survey of U.S. medical schools, announced earlier today, the magazine awarded its top ranking in pediatrics, for the second year in a row, to the physicians and scientists who work at The Children’s Hospital of Philadelphia.

This marks the 11th consecutive year that the program has been ranked first or second in the nation. We want to congratulate the faculty and staff of the Department of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania, CHOP’s academic partner, for this impressive recognition.

U.S.News recognized the Perelman School of Medicine at the University of Pennsylvania as the nation’s best pediatrics department, followed by Harvard University in second place and the University of Cincinnati in third. The university’s Department of Pediatrics is located here at Children’s Hospital.

The 2015 Best Graduate Schools rankings are based on two types of data: expert opinions about program excellence and statistical indicators that measure the quality of a school’s faculty, research and students. The data come from surveys of administrators at more than 1,350 programs and more than 13,500 academics and professionals, conducted during the fall of 2013 and early 2014. The rankings also took into account an institution’s research activity, reflected in grant awards to faculty from the National Institutes of Health.

We congratulate all who have worked so hard to sustain this impressive record of medical and academic excellence and thank them for the distinction they bring to CHOP through their efforts.

Permanent link to this article: http://www.research.chop.edu/blog/u-s-news-ranks-department-pediatrics-1-nation/

Mar 17 2014

New Gene Sequencing Test to Speed Donor Matching, Research

Gene SequencingGenetics experts at The Children’s Hospital of Philadelphia have developed a unique test to characterize the genes that encode HLA molecules. Relying on gene sequencing to type human leukocyte antigens (HLAs) — complex proteins that are essential to immune function — the new test has the potential to improve transplantation outcomes through refined donor compatibility assessments, and will expedite the donor selection process from bone marrow registries.

“This new test addresses a sixty-year-old problem,” said Dimitri Monos, PhD, director of the Immunogenetics Laboratory in the Division of Genomic Diagnostics. “Since the discovery of HLAs in the early 1950s, it has been a challenge to accurately and thoroughly characterize HLA gene sequences. We have now used next-generation sequencing tools to significantly advance HLA typing.”

The test also provides an advanced tool for research in immunological diseases, infectious diseases, and pharmacogenomics — the field that studies the influence of genetic variations on drug efficacy and toxicity. Children’s Hospital is the first hospital to offer this new comprehensive HLA typing test.

“This is a new, disruptive technology, with the potential to transform research and clinical practice, in transplantation and other fields,” said Robert Doms, MD, PhD, CHOP’s pathologist-in-chief.

HLA genes are the most complex gene family known in the entire human genome, and their sequences are highly variable, to a degree not adequately captured by conventional typing tests. Current tests often provide ambiguous and limited results, by sequencing only segments of HLA genes and failing to distinguish among different alleles suggested by a given sequence. In addition, preliminary testing often must be followed by a second level testing, adding expense and time to the HLA typing process.

The new test, says Dr. Monos, is a single test that provides the highest resolution possible by covering the full HLA genomic region. It can currently distinguish among 10,500 different alleles of all known HLA types and can fully characterize new alleles yet to be discovered. The researchers validated the test by comparing its results against previously sequenced data from a collection of over 300 samples characterized at five different genes.

CHOP will be offering the HLA typing test for patient testing as a service to medical and academic centers. The test is faster, more precise, and costs less than existing testing procedures. The new test’s most significant short-range impact may be in typing donors in bone marrow/stem cell registries.

“This faster, more thorough technology allows us to better account for subtle genetic differences between individuals,” said Dr. Monos. “We expect this knowledge to yield clinical benefits, by facilitating more precise matches between transplant donors and recipients, and assessing the significance of mismatches in genomic regions of the HLAs that were previously uncharacterized.”

To learn more about Children’s Hospital’s genetic testing services, see the Division of Genomic Diagnostics. For more information about the HLA typing test, see the full press release.

Permanent link to this article: http://www.research.chop.edu/blog/new-gene-sequencing-test-speed-donor-matching-research/

Mar 14 2014

Study Shows Normal Neurodevelopment Two Years After in Utero Surgery for Twin-Twin Transfusion Syndrome

TTTS_croppedThe Center for Fetal Diagnosis and Treatment at CHOP serves more than 150 families with complicated multiples pregnancies each year and performs more than 50 fetoscopic laser surgeries annually, one of the highest volumes of prenatal laser surgeries in the nation.

A multiyear study at CHOP looked at the neurocognitive effects of twin-twin transfusion syndrome (TTTS) in monochorionic twins who underwent in utero laser surgery. The study’s goal was to provide families more accurate information on what to expect before and after birth and to identify any long-term consequences.

“Overall, there were high rates of normal neurodevelopmental outcomes in these children at age 2,” said Nahla Khalek, MD, MPH, FACOG, a CHOP maternal-fetal medicine and clinical genetics specialist who led the study.

TTTS occurs before birth in about 10 to 15 percent of monochorionic twins who share one placenta but each have their own amniotic sac. The shared placenta contains blood vessels connecting both fetuses, and TTTS results from a blood flow imbalance. The smaller twin (donor) pumps blood to the larger twin (recipient), causing the recipient twin to receive too much blood and the donor to receive too little. Without intervention, TTTS results in the death of one or both fetuses in 80 to 100 percent of cases.

Dr. Khalek and colleagues analyzed two-year neurodevelopmental outcomes in 29 pairs of twins with TTTS who underwent selective laser photocoagulation (SLPC) of placental anastomoses in utero at CHOP between 2009 and 2011. This minimally invasive procedure uses a laser fiber inserted through a fetoscope to identify and disconnect all of the identifiable connecting blood vessels, allowing for redistribution and normalization of blood flow to each fetus.

The researchers assessed the children’s cognitive, language, behavior, and motor skills using three standard neurodevelopmental tests. The mean scores of all three tests were within or above average range or raised no concerns. They noted differences in some outcomes based on TTTS stage and whether or not a twin was a former donor versus former recipient.

“The risk of neurodevelopmental sequelae is low in TTTS with SLPC intervention,” the researchers concluded; however, Dr. Khalek suggested future research should follow neurodevelopmental outcomes as TTTS survivors reach school age.

“This data will allow us to further stratify patients and guide us in counseling parents about longer-term neurodevelopmental outcomes for their children,” Dr. Khalek said.

Laura and Adam Epstein, whose daughters, Rose and Madeline, were treated for TTTS by fetal surgeons at CHOP in 2011, and the Conway Family Foundation, a philanthropic organization run by the twins’ grandparents, provided funding for this study.

“This research is pioneering work that wouldn’t have happened without philanthropy,” Dr. Khalek said.

Dr. Khalek presented the study results at the annual meeting of the Society for Maternal-Fetal Medicine in New Orleans held Feb. 3-8.

In addition to Dr. Khalek, study authors from CHOP include Marsha Gerdes, PhD; Casey Hoffman-Craven, PhD; Anjani Villa, BS, CCRC; Okan Elci, PhD; Julie Moldenhauer, MD; Juan Martinez-Poyer, MD; and Mark P. Johnson, MD; as well as former CHOP physician Michael W. Bebbington, MD.

Permanent link to this article: http://www.research.chop.edu/blog/chop-researcher-sets-goals-new-istss-president-2/

Mar 12 2014

Why Can Commensal Organisms Cause Infections?

infectionThe human body is a very crowded place. In addition to human cells — which number approximately 37.2 trillion, according to a recent Annals of Human Biology paper — there are many, many more microbial cells that live in our bodies. Indeed, the NIH’s Human Microbiome Project notes “microbial cells are estimated to outnumber human cells ten to one,” including many that are commensal and live in perfect harmony with our own cells.

But sometimes these commensal microbes can cause disease, in particular when they leave their normal environment and spread to other sites. One Children’s Hospital researcher, Joseph W. St. Geme, III, MD, CHOP’s Physician-in-Chief and Chair of the Department of Pediatrics at the University of Pennsylvania, has spent much of his career working to better understand how this transition can happen.

For many years Dr. St. Geme has been examining host-pathogen interactions, with a particular focus on the bacterium Haemophilus influenzae. Despite its somewhat misleading name, H. influenzae does not cause influenza, but is instead associated with invasive infections and localized respiratory tract disease. More recently, Dr. St. Geme has initiated studies of Kingella kingae, an emerging cause of bone and joint infections in young children.

H. influenzae and K. kingae are members of the normal bacterial flora, as H. influenzae is located in the nasopharynx and K. kingae in the posterior pharynx. “Up to 70 percent or so of children in their first few years of life are colonized at some point with each of these organisms,” Dr. Geme noted.

Both Dr. St. Geme’s H. influenzae and K. kingae research projects are “investigations of host-pathogen interactions and focus on understanding how bacteria that are common, commensal organisms, usually not associated with disease, in some circumstances produce disease,” he said.

Despite the fact that K. kingae is common in young children, the bacterium has only been appreciated as an important pathogen within the last fifteen years, and is a leading cause of bone and joint infections in children younger than 3 or 4 years of age, Dr. St. Geme said. A recent award from the National Institute of Allergy and Infectious Disease is allowing Dr. St. Geme to build on his earlier K. kingae research, with investigations that he hopes will lead to “an improved understanding of the pathogenesis of disease … and will lay the foundation for developing a capsule-based vaccine.”

“If we understand the bacterial determinants of the initial stages of infection, which are fundamental to the development of disease, we can use this information to develop new vaccines to prevent disease” Dr. St. Geme said. “Alternatively, we can use this information to develop novel antimicrobials that target bacterial factors required for infection.”

Read more about Dr. St. Geme’s work in Bench to Bedside.

Permanent link to this article: http://www.research.chop.edu/blog/can-commensal-organisms-cause-infections/

Mar 10 2014

As One Food Allergy Resolves, Another May Develop

food allergy

Food allergies to milk, egg, soy, and wheat have been linked to eosinophilic esophagitis.

Some children who outgrow one type of food allergy may then develop another type of allergy, more severe and more persistent, to the same food. A new study by pediatric allergy experts suggests that healthcare providers and caregivers carefully monitor children with food allergies to recognize early signs of eosinophilic esophagitis (EoE), a severe and often painful type of allergy that has been increasing in recent years.

“These two types of allergy have some elements in common, but patients with EoE usually don’t go on to develop tolerance to the foods that trigger EoE,” said pediatric allergist Jonathan M. Spergel, MD, PhD, of The Children’s Hospital of Philadelphia (CHOP). Dr. Spergel directs CHOP’s Center for Pediatric Eosinophilic Disorders, one of the nation’s premier programs for these conditions.

Only recently recognized as a distinct condition, EoE involves swelling and inflammation of the esophagus, along with excessive levels of immune cells called eosinophils. Often painful, EoE may cause weight loss, vomiting, heartburn, and swallowing difficulties. EoE can affect any age group, but it is often first discovered in children experiencing feeding difficulties and failure to thrive.

Dr. Spergel’s team compared EoE with IgE-mediated food allergy — the more familiar type of food allergy that occurs when antibodies mount an exaggerated immune response against proteins in particular foods. Nuts, eggs, or milk, for example, may trigger hives, other skin reactions, vomiting, or other symptoms.

The researchers performed a retrospective analysis of all children seen at CHOP for EoE between 2000 and 2012, a total of 1,375 patients. Of that number, 425 researchers identified a definite food causing their condition — most commonly milk, egg, soy, and wheat. Within that subgroup, 17 patients had developed EoE to a food after having outgrown IgE-mediated allergy to that specific food.

“The pattern we found in those 17 patients suggests that the two types of food allergy have distinct pathophysiologies — they operate by different mechanisms and cause different functional changes,” Dr. Spergel said. “However, this pattern also raises the possibility that prior IgE-mediated food allergy may predispose a patient to developing EoE to the same food.”

Dr. Spergel added that approximately 10 percent of patients who undergo desensitization therapy for IgE-mediated foods allergies subsequently develop EoE to the same food — a fact that healthcare providers should consider in managing care for patients with food allergies. In desensitization therapy, a clinician exposes a patient to miniscule amount of an allergy-producing food, then gradually increases the amount, aiming for the patient to become tolerant to that food.

Dr. Spergel is the senior author of the research, presented recently by Solrun Melkorka Maggadottir, MD, also of CHOP, at the annual meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) in San Diego.

Permanent link to this article: http://www.research.chop.edu/blog/one-food-allergy-resolves-another-may-develop/

Mar 07 2014

$3.25 Million Gift Creates Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence

Friedreich's AtaxiaThree longtime allies have joined forces to create the new Penn Medicine/CHOP Friedreich’s Ataxia Center of Excellence. The establishment of the center was catalyzed by a $3.25 million gift from the Friedreich’s Ataxia Research Alliance (FARA), in partnership with the Hamilton and Finneran families.

Friedreich’s ataxia (FA) is a progressive neurogenetic condition found in approximately 1 in 50,000 people worldwide. While relatively rare, it is the most common form of inherited ataxia, a condition characterized by progressive lack of coordinated movement and loss of balance. FA also involves degeneration of heart muscle and nerve cells. Symptoms usually begin in childhood, and most patients are confined to a wheelchair by their mid-to-late twenties. Myocardial failure and/or arrhythmias are the most common cause of premature death. Currently there are no approved drugs to treat FA.

For the past 16 years Penn Medicine, The Children’s Hospital of Philadelphia (CHOP), and FARA, a nonprofit organization dedicated to curing FA, have collaborated to provide and push forward the care needed by FA patients.

FARA, CHOP, and Penn Medicine have also shared in research and clinical trials that have elucidated the metabolic dysfunction underlying FA. Their work has created a database of well-documented patients and a pipeline of more than 20 drug candidates ready to be mined for new therapies. Today the FA clinical program at CHOP is the largest in the world.

The new Center’s team is working with pharmaceutical industry partners to develop drug candidates as well as biomarkers for FA, and this effort fits alongside a broader initiative at Penn Medicine: a gift from an anonymous donor recently founded the Center for Orphan Disease Research and Therapy to support the pursuit of novel therapies for rare diseases of all kinds.

The Friedreich’s Ataxia Center of Excellence is co-directed by David Lynch, MD, PhD, FA program director at CHOP, and Robert B. Wilson, MD, PhD, professor of Pathology and Laboratory Medicine at the Perelman School of Medicine. Drs. Lynch and Wilson both serve on FARA’s Scientific Advisory Board, and Dr. Wilson was a founding member of FARA’s board of directors and first chairman of its Scientific Review Committee.

The early goals and objectives of the Center include:

  • Adding cardiac expertise in FA research and clinical care under the leadership of Kimberly Y. Lin, MD, a cardiologist at CHOP with board certification in pediatrics, internal medicine, and pediatric cardiology.
  • Increasing capacity for and opening more clinical trials.
  • Creating a dedicated drug discovery unit.
  • Exploring new basic research avenues using micro RNA and epigenetics approaches.
  • Establishing a biomarker development program with the expertise of Ian Blair, PhD, of the Perelman School of Medicine.

“Integrating cardiac expertise into the care of patients is one major step forward this gift allows us to pursue,” says Philip R. Johnson, MD, executive vice president and chief scientific officer at CHOP. “Rare diseases are often an area where philanthropy can make a difference, and the generosity of these donors will make a significant impact.”

Additional information about the new Friedreich’s Ataxia Center of Excellence is available here.

Permanent link to this article: http://www.research.chop.edu/blog/3-25-million-gift-creates-penn-medicinechop-friedreichs-ataxia-center-excellence/

Mar 06 2014

New Gene Signals Likely Blood Pressure Drug Targets

blood pressureThe list of genes affecting blood pressure is expanding, as researchers pursue likely targets for therapeutics already in existence or in development. A Children’s Hospital researcher collaborated with an international study team that discovered 11 novel genetic signals associated with blood pressure levels and confirmed 27 previously discovered genetic signals.

High blood pressure, or hypertension, is a complex condition and a well-known risk factor for heart disease, stroke, peripheral artery disease, and chronic kidney disease. A substantial need for improved blood pressure medicines exists because not all patients respond well to current treatments, and other patients require combinations of three or more drugs.

Most of the new genetic signals that Brendan J. Keating, DPhil, a geneticist with The Center for Applied Genomics (CAG) at The Children’s Hospital of Philadelphia, and the study’s co-authors identified are “druggable” targets that offer the possibility of expedited pharmaceutical development of therapeutics for high blood pressure.

“Some of the protein targets already are targets of existing drugs for other diseases, while others are the focus of drugs currently in early-phase clinical trials or under preclinical development,” Dr. Keating said.

In the study that appeared online in the American Journal of Human Genetics, the researchers performed a discovery analysis of DNA from more than 87,000 individuals of European ancestry. They assessed their initial findings in a replication test, using an independent set of another 68,000 individuals.

Then the researchers used pharmacological databases to analyze potential targets in the discovered genetic region. They found that gene products associated with 10 of the genes were predicted to be targets for small-molecule drugs. In fact, two genes — KCNJ11 and NQO1 — are currently targeted by existing approved drugs.

“If clinicians can reposition existing drugs to treat some patients with hypertension, this will save significant time in drug development, as they won’t be starting development from scratch,” Dr. Keating said.

He added that even with possible repositioning, more research is needed to determine which drug candidates are effective against hypertension, possibly in personalized treatments based on patients’ genetic makeup.

Dr. Keating is the lead clinical data analyst at CAG, one of the world’s largest programs for detecting gene variations and linking them to particular illnesses, and the only such program entirely based at a pediatric hospital. In addition to his position at CHOP, Dr. Keating is a faculty member of the Department of Pediatrics and the Division of Transplantation in the Department of Surgery in the Perelman School of Medicine at the University of Pennsylvania.

For this study, Dr. Keating collaborated with two senior co-authors, Folkert W. Asselbergs, MD, PhD, of University Medical Center Utrecht, the Netherlands, and Patricia B. Munroe, PhD, of Queen Mary University, London, U.K. Other study co-authors were from the U.S., the U.K., the Netherlands, Canada, Germany, Sweden, and Ireland.

Study funders included the National Heart, Lung and Blood Institute; the British Heart Foundation; and the Netherlands Organisation for Health Research and Development.

Permanent link to this article: http://www.research.chop.edu/blog/new-gene-signals-likely-blood-pressure-drug-targets/

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