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/

Mar 04 2014

CHOP Neuroscientist Advocates for Federal Concussion Support

concussionIn an example of how many CHOP researchers’ work isn’t confined to the laboratory, Children’s Hospital Neuroscientist Akiva S. Cohen, PhD, recently traveled to Washington, DC to discuss concussion treatment strategies and to advocate for increased federal support for concussion research. A concussion and traumatic brain injury (TBI) researcher, Dr. Cohen investigates brain injuries’ underlying cellular and molecular mechanisms.

According to the CDC, roughly 2 million TBIs occur every year in the U.S, and more than 500,000 TBIs are suffered by children aged 14 years and younger. While many reported TBIs are milder forms such as concussions, even “mild” brain injuries can lead to long-term health challenges, such as cognitive and emotional issues.

Recently, there has been increased scrutiny on the effect of concussions on athletes — and football players in particular — of all ages. In October of 2013, the Institute of Medicine and the National Research Council released an extensive report on sports-related concussions in children and teens that found helmets do not prevent concussions in youth athletes. The report, which was authored by a committee of experts, including the Center for Injury Research and Prevention’s Kristy Arbogast, PhD, also found that despite increased awareness of concussions, there remains a culture “that resists both the self-reporting of concussions and compliance with appropriate concussion management plans.”

While in Washington, DC, Dr. Cohen met with Philip Rubin, PhD, the Office of Science and Technology’s (OTSP) principal assistant director for Science and assistant director for Social, Behavioral, and Economic Sciences. Part of the executive branch administration, the OTSP was founded to “advise the President and others within the Executive Office of the President on the effects of science and technology on domestic and international affairs,” according to the OTSP’s website.

In addition to discussing concussion treatment strategies — including Dr. Cohen’s investigation of using a cocktail of key amino acids to treat sleep issues following concussion — Drs. Cohen and Rubin also discussed the impact the BRAIN initiative might have on concussion and TBI research.

The NIH’s budget also came up, as the agency’s most recent appropriation was solidified in the $1.1 trillion spending bill President Obama signed into law January 17. The NIH’s appropriation of $29.9 billion in the “Consolidated Appropriations Act, 2014” was lower than the $31.3 billion President Obama had requested, leading to calls for increased spending.

“I enjoyed the chance to travel to DC to meet with Dr. Rubin and the administration to discuss concussion and TBI care,” said Dr. Cohen. “As our understanding of the mechanisms of concussions improves, new avenues of research will continue to be opened. Robust, ongoing federal support for research is integral to advancing novel treatment strategies.”

To learn more concussions, and about The Children’s Hospital of Philadelphia’s concussion care and research, see the Hospital’s webpage and the Center for Injury Research and Prevention. To learn more about Dr. Cohen’s research, see the CHOP Research blog.

Permanent link to this article: http://www.research.chop.edu/blog/chop-neuroscientist-advocates-federal-concussion-support/

Feb 27 2014

Campaign Raises Awareness of Pediatric Palliative Care

170079916_croppedPediatric palliative care is a powerful intervention that can be prescribed alongside curative or life-prolonging therapies for children with serious illnesses. Research has shown that pediatric palliative care services can help reduce a child’s pain, help manage other distressing symptoms, and provide emotional support.

At Children’s Hospital of Philadelphia, a nationally esteemed Pediatric Advanced Care Team (PACT) takes a comprehensive approach that focuses on psychological, social, and spiritual needs as a standard part of palliative care. Yet many families and caregivers elsewhere are not as familiar with palliative care’s benefits, and health care providers hesitate to recommend palliative care for their youngest patients.

Each year, more than 45,000 children die in the U.S., and three-quarters of these deaths occur in the hospital setting. The National Institute of Nursing Research (NINR) recently launched a national campaign, “Palliative Care: Conversations Matter,” to raise awareness of palliative care and increase its use within the pediatric population.

The NINR, a component of the National Institutes of Health, brought together parents, palliative care clinicians, and scientists to develop evidence-based materials designed to initiate dialogues about palliative care soon after diagnosis and throughout the course of an illness. Chris Feudtner, MD, PhD, MPH, director of research for PACT, was involved in planning the NINR campaign and has had several research studies funded by NINR grants, including an ongoing two-year cohort study focusing on decision-making in advanced pediatric care.

“Part of what the campaign addresses is concerns that parents may view the introduction of palliative care as an ominous sign that the medical team is stepping back,” Dr. Feudtner said. “Palliative care is not exclusive to patients who are no longer seeking cure or no longer seeking life-prolonging therapy. It can be in addition to those type of therapies. The campaign can help physicians provide a more clear explanation of what palliative care is and allay fears.”

The Palliative Care: Conversations Matter campaign materials include informational video vignettes and tear-off pads of patient education sheets that guide providers in how to engage in interactive palliative care discussions. The NINR has received requests for these resources from across the U.S. and internationally.

“The response has been excellent so far,” according to NINR Director Patricia A. Grady, MD. “We’ve been pleased to see so many colleagues in palliative care and nursing organizations helping us spread the word.”

An important part of implementing the campaign is having skilled staff as ambassadors at the bedside to collaborate with parents and incorporate their perspectives into the palliative care plan, Dr. Feudtner said. CHOP’s PACT, for example, helps families understand their children’s underlying disease process and prognosis, optimize symptom control, establish a comforting environment, and promote their highest quality of life.

“You need to have high quality palliative care teams in place in order to make a bad situation as good as possible,” Dr. Feudtner said.

A study he published in the December issue of Pediatrics showed an explosion in the number of palliative care teams over the past 10 years in the U.S. Of 162 children’s hospitals that provided data for the study, 69 percent reported having a pediatric palliative care program.

“NINR’s campaign will help raise awareness of and demand for pediatric palliative care among health care providers and patients, which we hope will encourage the continued growth in research in this important field,” Dr. Grady said.

Dr. Feudtner’s current research aims to improve understanding of how parents make extremely difficult medical decisions for children with life-threatening complex chronic conditions. The findings of his previous studies have emphasized the importance of psychology and the emotional realities involved in this daunting challenge.

Building on research papers published in 2010 and 2012 describing decision-making by parents of children receiving palliative care consultative services, the current CHOP cohort study is following 200 parents and 163 children. Dr. Feudtner and colleagues are examining the process of decision-making longitudinally and the impact on decision-making of hopeful patterns of thought, positive and negative affect, and the child’s illness trajectory.

“Our team and our experience at CHOP have helped us to heed the potential of what palliative care can do from many different angles,” Dr. Feudtner said. “And our research is taking us further. We have bedside learning from clinical practice intermixing with and informing health services and epidemiological research.”

Dr. Feudtner recently received the 2014 Hastings Center Cunniff-Dixon Physician Award in the mid-career category. Presented annually, the award recognizes five physicians who have distinguished themselves in advancing the practice of palliative care and model exemplary skill and compassion at the bedside. He also is associate professor of pediatrics in the Perelman School of Medicine at the University of Pennsylvania and the Steven D. Handler Endowed Chair of Medical Ethics at the Children’s Hospital of Philadelphia.

Permanent link to this article: http://www.research.chop.edu/blog/campaign-raises-awareness-pediatric-palliative-care/

Feb 25 2014

Research Advocates Dispirited Over Omnibus Funding Level for NIH

97788738Biomedical research advocates had hoped that a surge in research and development funding in the 2014 budget would be the best medicine for the National Institutes of Health, which has been impaired by mandated across-the-board sequestration cuts. Instead, the $1 billion increase slated for NIH in the $1.1 trillion appropriations bill passed by Congress in January was a bitter pill.

While the boost will bring NIH’s 2014 research and development budget to an estimated $29 billion, it remains “well below the level of scientific opportunity,” warned Mary Woolley, president and CEO of Research!America.

“The omnibus has failed to fund NIH at a level that fully reverses the impact of sequestration on the agency’s baseline funding level, much less establishes a growth trend that can fully unleash the potential inherent in the sequencing of the human genome and other research breakthroughs,” Woolley wrote in a statement.

The omnibus bill funds the government through Sept. 30. Congress reached the spending deal in December, but it took a month for lawmakers to divvy up discretionary dollars in the 1,500-page bill that rolls multiple department budgets — defense and non-defense accounts — into one. President Obama signed it into law Jan. 17.

For many governmental agencies, the 2014 budget eased the pain of the 2013 sequester’s 5 percent bite; however, the majority of the 27 institutes and centers under the NIH’s umbrella remain underfunded. NIH funding for research and development is now 2.2 percent below fiscal year 2012 levels, a loss of roughly $700 million, according to estimates by the American Association for the Advancement of Science (AAAS).

Carrie Wolinetz, PhD, president of United for Medical Research, agreed that the $1 billion increase falls short of sustainable funding levels for NIH to accomplish its mission of turning scientific discoveries into better health.

“The proposed package won’t adequately reverse the damage done by last year’s budget sequester and ensure the nation’s biomedical research enterprise makes continued progress in lifesaving research and development,” Dr. Wolinetz stated.

Sequestration resulted in approximately 640 fewer competitive research project grants that were issued in fiscal year 2013 compared to fiscal year 2012, according to the NIH. The 2014 funding levels will gain back some ground for emerging investigators. The NIH would be able to continue all current research programs and begin approximately 385 additional research studies and trials, according to a statement from appropriators.

Yet, many stalled projects will need to seek other funding sources. Delays in medical progress not only put Americans’ health in jeopardy, but they also add to their economic risks, research advocates stressed. For example, the medical innovation sector currently employs 1 million U.S. citizens, according to the NIH, and ongoing funding declines could discourage young scientists who will play a pivotal role as global competitiveness in research and development ramps up.

In an editorial for the Washington Post, NIH Director Francis S. Collins, MD, PhD, worried that “years of effectively flat funding for biomedical research have left scientists facing the lowest chances in history of having their research funded by NIH. Many young scientists are on the verge of giving up, taking with them the talent needed to make tomorrow’s medical breakthroughs.”

In constant dollars, the NIH budget has come down by around 15 percent since fiscal year 2004, according to the AAAS analysis.

“The nation’s federal investment in science as a share of the economy currently stands at 0.82 percent — the lowest point in 50 years,” wrote Alan I. Leshner, chief executive office of the AAAS, and Paul Stoffels, MD, chief scientific officer and worldwide chairman of pharmaceuticals at Johnson & Johnson, in an op-ed article for Politico Magazine.

While praising Congress’s bipartisan efforts to put an end to forced budget cuts and fights over discretionary funding, the progress “will not counteract the decades-long decline in federal funding for research and development that is so essential to our economic future and critical to accelerating treatments for today’s major health care challenges.”

Here’s how the NIH’s $1 billion funding increase stacked up against the amounts that some of other public health and scientific agencies won in the 2014 spending package:

  • The National Aeronautics and Space Administration landed one of the bigger increases. It received $17.7 billion, including a 7.7 percent jump to $5.2 billion for its science program.
  • The bill provided $7.2 billion for the National Science Foundation, an increase of 4.2 percent ($288 million) above the fiscal year 2013 sequester level.
  • The Centers for Disease Control and Prevention (CDC) also fared well, growing its budget to $5.8 billion, which went up by $370 million from 2013. Among its top spending priorities in its fiscal 2014 budget request, the CDC wants to boost spending for vaccines for children.

Attention now turns to the 2015 budget cycle, which begins Oct. 1. The White House announced that it will release President Barack Obama’s budget for fiscal year 2015 on March 4. House and Senate leaders are hopeful that the momentum they built during the appropriations process will continue so that they can enact a detailed funding plan before the October deadline.

Permanent link to this article: http://www.research.chop.edu/blog/research-advocates-dispirited-omnibus-funding-level-nih/

Feb 21 2014

CHOP Research Leader Contributes to Study Showing New Approach to Vaccines against Dangerous Viruses

Johnson, Phil_2014_Blog_CroppedThe Children’s Hospital of Philadelphia Research Institute’s chief scientific officer, Philip R. Johnson, MD, is among the co-authors of a new study that presents an advanced approach to vaccine design. This innovation, in which artificial proteins are custom-designed as vaccine components, offers the promise of a new way to prevent serious childhood infections caused by respiratory syncytial virus (RSV). More broadly, it may enable the creation of new vaccines against evolving, difficult-to-treat diseases such as HIV, influenza and hepatitis C.

The study, which was published recently online in Nature, was led by William R. Schief, PhD, and colleagues from The Scripps Research Institute (TSRI) in La Jolla, Calif. “This was a proof-of-principle demonstration of a technology that could be very useful against HIV, influenza and other highly variable viruses that have been difficult to stop using traditional vaccine-design strategies,” said Dr. Schief.

Most existing vaccines use inactivated viruses or similar particles to stimulate the body’s immune system to release infection-fighting antibodies. However, rapidly evolving infectious agents such as HIV have been able to change quickly enough to evade traditional vaccine candidates. As a result, vaccine experts have been working to design new vaccines to elicit broadly neutralizing antibodies that strike against hidden vulnerable structures within quick-changing viruses.

The new strategy uses sophisticated techniques to imitate an epitope — a structure specific to each type of invading virus that is recognized by the immune system. The scientists used a new software application, which they call “Fold from Loops,” to design flexible protein scaffolds to hold the epitope that induces the immune system to produce protective antibodies.

In Nature study, the research team induced potent antibodies in non-human primates against RSV, which commonly makes human babies sick, and kills large numbers of infants worldwide. According to the CDC, each year in the U.S. between 75,000 and 125,000 children under the age of 1 are hospitalized with RSV infections.

The investigators’ successful experiment offers proof-of-principle that this approach is feasible for developing a first RSV vaccine in humans, as well as for developing potential future vaccines against HIV, influenza and hepatitis C.

This work builds on previous laboratory research by Dr. Johnson aimed at finding innovative methods in vaccine design. In 2009, for example, his team published a study in Nature Medicine that used gene therapy to produce antibody-like proteins to protect monkeys from the animal counterpart to HIV. And in May of 2013, Dr. Johnson contributed to a Science study calling for a “Human Vaccines Project” to accelerate the development of new vaccines. In the current study, he performed laboratory experiments using his collaborators’ newly designed proteins.

The Nature study “represents the confluence of recent technological advances in computational biology, structural biology and immune monitoring, and offers great potential for accelerating development of next generation vaccines against major global diseases,” said Senior Vice President and Chief Scientific Officer the International Aids Vaccine Initiative Wayne C. Koff, PhD.

“Bringing these new types of vaccines into clinical use will take years of work, but this study represents an important first step along the way,” noted Dr. Johnson.

To read more about this groundbreaking study, see TSRI’s press release or Nature.

Permanent link to this article: http://www.research.chop.edu/blog/chop-research-leader-contributes-study-showing-new-approach-vaccines-dangerous-viruses/

Feb 19 2014

Study Leads to Increased Heart Disease Risk Understanding

166840493Most of us have heard of the “good cholesterol” and “bad cholesterol” coursing through our bloodstream. In the conventional wisdom of the past 30 years, having more of the “good” variety — high-density lipoprotein, or HDL — can lower your risk of heart disease, while more “bad” cholesterol — low-density lipoprotein, or LDL — increases your risk. Indeed, over the years, clinical trials and other studies have found that drugs that lower LDL also lower your probability of heart disease.

However, trials have not shown heart-health benefits to increasing HDL or to lowering triglycerides, a third type of blood lipid. But now a new study from The Children’s Hospital of Philadelphia and the University of Pennsylvania, published recently in European Heart Journal, sheds light on the role of genes and blood lipid levels in cardiovascular health. Newer tools for gene analysis show how variations in DNA are underlying actors affecting heart disease, a major worldwide cause of death and disability.

“Now we are able to pinpoint gene signals that actually cause some of these conditions,” said geneticist Brendan J. Keating, DPhil, of The Center for Applied Genomics. “Unraveling how genetic variants that influence lipid traits are related to heart disease risk is a step toward designing treatments.” Dr. Keating collaborated with University of Pennsylvania clinical epidemiologist Michael V. Holmes, MD, PhD.

The investigators used a recently developed tool called Mendelian randomization (MR), which analyzes genetic variations using a method that identifies genes responsible for particular diseases, independent of confounding factors such as differences in behavior or environmental influences that often limit the conclusions of epidemiology research.

The researchers analyzed DNA data from 17 studies including over 60,000 individuals, of whom more than 12,000 had experienced coronary heart disease, including heart attacks. They confirmed that higher levels of LDL, the “bad cholesterol,” were more likely to cause heart disease. But there were new results: high levels of triglyceride also caused higher risk of heart disease. At the same time, there was little evidence that higher levels of HDL, the “good cholesterol,” had a protective effect.

The novelty of their approach, say the authors, lies in their use of a gene score MR analysis using individual participant data. These results build on previous findings and help clarify in further detail the separate roles of triglycerides and HDL in risk for coronary heart disease.

“These findings are important in understanding which blood lipids cause heart disease, and will enable clinicians to better target those lipids with drugs to reduce the risk of heart disease,” noted Dr. Holmes.

To read more, see the European Heart Journal study, or the full press release about the investigation.

Permanent link to this article: http://www.research.chop.edu/blog/study-leads-increased-heart-disease-risk-understanding/

Feb 13 2014

Alex’s Lemonade Stand Foundation Grant Supports CHOP Childhood Cancer Research Project

Alex's Lemonade StandOne in every 691 babies in the U.S. is born with Down syndrome, according to the National Down Syndrome Society, and have a predisposition for a certain kind of cancer. A Children’s Hospital hematologist, Stella T. Chou, MD, will receive $100,000 over the course of one year to fund her research on how an extra chromosome 21 and mutations in a transcription factor gene called GATA1 affect blood development, creating a predisposition to leukemia in children with Down syndrome.

A new Springboard Grant awarded by Alex’s Lemonade Stand Foundation will jumpstart the project, which fell short of funding due to sequester cuts within the National Institutes of Health.

For fiscal year 2013, the sequestration required NIH to cut 5 percent or $1.55 billion of its budget. In response to the budget reduction, Alex’s Lemonade Stand Foundation stepped in to advance new projects with high impact potential, such as Dr. Chou’s investigation.

“With less than 5 percent of the federal government’s total funding for cancer research each year being dedicated to childhood cancers, Alex’s Lemonade Stand Foundation is dedicated to keeping promising research alive,” stated Jay Scott, co-executive director of the foundation, in a Dec. 19 press release announcing the award. “Through the Springboard Grant, we work to sustain the research of these promising investigators while they reapply for large-scale funding, ultimately resulting in better treatments and cures for all childhood cancers.”

Dr. Chou’s research project aims to “provide new insights into blood cell production, generate new experimental tools for the biomedical community, and elucidate new strategies to study inherited blood diseases.”

Children with Down syndrome are predisposed to “a unique constellation of blood diseases,” Dr. Chou said. These include an increase in total red blood cell mass and a decrease in the number of platelets. In addition, about 10 percent of neonates with Down syndrome are born with preleukemia known as transient myeloproliferative disorder (TMD), which spontaneously resolves in most cases. However, 20 percent of patients with TMD subsequently develop acute megakaryoblastic leukemia (AMKL) by age 5, which responds well to chemotherapy but is associated with significant treatment-related toxicity.

In order to figure out how TMD and AMKL occur, Dr. Chou’s research team will trace the formation and development of blood cells from their early beginnings during embryogenesis and then define how they go awry. They will focus on how two potential culprits — mutations in GATA1 and genes on chromosome 21 (HSA21) — act separately and together to modulate hematopoiesis.

The investigators will use a novel approach that involves the creation and manipulation of patient-derived induced pluripotent stem cells (iPSCs) for the study of genetic disease. iPSCs are a renewable human cell source that can recapitulate the multiple stages of blood formation. They are an alternative to human samples, which are difficult to obtain in sufficient quantities for scientific investigation.

Cancer is the leading cause of death by disease among U.S. children between infancy and age 14, according to the National Cancer Institute. Approximately 11,600 new cases of pediatric cancer are expected to be diagnosed in children ages 0 to 14 years in 2013. Alex’s Lemonade Stand Foundation has raised more than $65 million toward finding a cure for all children with cancer, funding more than 350 pediatric cancer research projects nationally.

Permanent link to this article: http://www.research.chop.edu/blog/alexs-lemonade-stand-foundation-grant-supports-chop-childhood-cancer-research-project/

Feb 11 2014

Neurologist Receives Award to Study Cell-Based Epilepsy Treatment

160248924The Children’s Hospital of Philadelphia’s Ethan Goldberg, MD, PhD, recently received an award from the epilepsy advocacy organization Citizens United for Research in Epilepsy (CURE) to study using transplanted cells to treat epilepsy. Dr. Goldberg was one of three researchers to receive a “Taking Flight” award, a one-year grant of up to $100,000 designed to “promote the careers of young investigators and support them as they develop an independent research focus,” according to CURE.

A brain disorder marked by seizures of varying intensity and type, epilepsy affects approximately 2 million Americans. And per the CDC, roughly 10 percent of the U.S. population — around 31 million people — will experience a seizure during their lifetime. Seizures associated with epilepsy range from short absence seizures to generalized tonic clonic, or grand mal, seizures. These whole body seizures involve loss of consciousness, incontinence, and potentially violent convulsions.

While its cause is sometimes unknown, epilepsy can be brought on by an injury or a medical condition, such as a brain tumor or infection. Though there is no cure for epilepsy, about 70 percent of those who have the disease can have their seizures controlled with medication, according to the National Institute of Neurological Disorders and Stroke. But for many, epilepsy is a lifelong condition.

CURE was founded by parents of children with epilepsy to “spearhead the search for a cure” by raising money to support epilepsy research. Dr. Goldberg’s project is an investigation of using “specific, defined subtypes of cortical interneuron precursors to treat epilepsy and its comorbidities in an experimental model of acquired chronic temporal lobe epilepsy.” Dr. Goldberg has been working with Children’s Hospital’s Stewart A. Anderson, MD, Associate Professor and Research Director of Child Psychiatry at CHOP, as well Jennifer Tyson, a graduate student in Dr. Anderson’s laboratory.

With this investigation, the researchers hope to discover novel treatments for forms of epilepsy that are resistant to standard medication.

“A large component of our epilepsy practice here at CHOP is the care of patients with severe, medically intractable epilepsy, either acquired epilepsy secondary to brain injury or due to a genetic cause,” said Dr. Goldberg. “Cell-based therapies offer hope of a future cure for our patients who are in greatest need, although significant additional basic science research is required to realize this potential. This generous grant from CURE will greatly assist in getting this project off the ground and pushing it forward.”

The Children’s Hospital of Philadelphia has a robust epilepsy treatment and research program. Part of Children’s Hospital’s Division of Neurology, the Pediatric Regional Epilepsy Program’s multidisciplinary team of clinicians, nurse practitioners, and researchers works with families to design personalized treatment plans that best control epilepsy with as few side effect as possible.

To learn more about the Pediatric Regional Epilepsy Program, see the Hospital’s website.

Permanent link to this article: http://www.research.chop.edu/blog/neurologist-receives-award-study-cell-based-epilepsy-treatment/

Feb 06 2014

Collaborations Set to Advance the Healthcare of Children

IMG_5455Along with its research partners Drexel University and Hebrew University of Jerusalem, The Children’s Hospital of Philadelphia Research Institute recently hosted a collaborative research symposium that gave researchers from all three institutions the chance to connect and share ideas.

The Advancing Healthcare for Children symposium, held Jan. 27-29 brought together investigators for presentations, discussions, and networking events.

Announced in November, the research agreement between Children’s Hospital, Drexel University, and Hebrew University will focus on pediatric translational research and moving investigations from the bench to the bedside. One of the goals of the symposium was to form collaborative “Dream Teams” of investigators who would unite to craft innovative solutions to challenges.

Saying in his opening remarks that “we must dare to cross disciplinary and national boundaries” to meet unmet medical needs, John A. Fry, president of Drexel University, noted “our job is to take bold steps” and break through barriers.

IMG_5428The symposium also featured a visit from Philadelphia Mayor Michael Nutter. The research agreement between Children’s Hospital, Drexel University, and Hebrew University came about in part due to a trade mission Mayor Nutter led to Israel in November 2013. CHOP and Drexel’s “partnership with Hebrew University will allow all three parties to share research and ultimately improve children’s healthcare,” said Mayor Nutter when the agreement was signed.

And on the opening day of the symposium, after proudly noting that Children’s Hospital was “the best children’s hospital in the U.S.,” Mayor Nutter said that he could think of no better place to celebrate such a “tremendous collaboration.”

The symposium featured sessions on everything from the nervous system to orphan diseases to pediatric cancers and drug discovery. In addition to several plenary sessions, concurrent breakout sessions on topics such as nervous system disorders, nanomedicine, gene therapy, and autoimmunity promoted dialogue and collegiality between experts.

For example, during the session “Transformative Approaches to Diseases and Disorders of Childhood,” Director of CHOP Research Philip R Johnson, MD, said that defining the future of pediatric medicine “is a tall challenge.” But in Dr. Johnson’s talk, he challenged researchers to consider the interplay of genomics and microbiomes, as they considered ways to advance pediatric care.

IMG_5362Over the course of the symposium, investigators from all three organizations presented. Researchers from Children’s Hospital included Robert J. Levy, MD, Stewart Anderson, MD, Hakon Hakonarson, MD, PhD, and Marni Falk, MD. Drexel University’s representatives included Kenny Simansky, PhD, Amir Toib, MD, and Sriram Balasubramanian, PhD, while a number of Hebrew University investigators attended, including Rami Yaka, PhD, Eylon Yavin, PhD, and Galia Blum, PhD.

On the final day of the symposium, participants were given the opportunity to meet with meeting participants privately for one-on-one discussions. These meetings allowed investigators to follow up on presentations and discussions, and served as the first step in the development of new collaborations.

“The symposium really exceeded our expectations,” said CHOP Research’s Deputy Scientific Director Tom Curran, PhD, FRS, who led the organization of the symposium. “It set the tone for us to work together, transcending traditional boundaries, and forming unique collaborations with the common theme of improving the health and welfare of children.”

The investigators will continue their discussions in the coming weeks and work to develop and hone various “Dream Teams” to tackle pediatric diseases.

To learn more about the Advancing Healthcare for Children symposium, see the symposium’s website.

Permanent link to this article: http://www.research.chop.edu/blog/collaborations-set-advance-healthcare-children/

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