February 11, 2019

The Clinical Research Center/Research Resources Office presented the Clinical Research Award for First Quarter 2019 to Ruth Eser-Jose, research coordinator with the Immunology, Allergy, Rheumatology and Retrovirology (IARR) Department.

This award was established by the Clinical Research Center in collaboration with the Research Resources Office to recognize and honor individual contributions to protecting the best interest of the research subjects and compliance with applicable rules and regulations.

Eser-Jose first joined Texas Children’s Hospital in 2005 and worked in the General Clinical Research Center (GCRC) as a staff nurse. She later transitioned in 2015 to her current role with IARR. Her research activities in the CRC focus on coordination and management of research participants in the Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials Network (IMPAACT) Cohort HIV studies.

October 29, 2018

Some of the brightest minds in neuroscience recently converged on the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital for its fourth biennial symposium and workshop, in partnership with Baylor College of Medicine.

The special two-day event brought together nearly 300 physicians, scientists, patients, patient advocacy groups, pharmaceutical industry experts and leaders from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke, and the National Institute for Mental Health, to address key issues in the field of neuropsychiatry, an intersectional branch of medicine that deals with mental illnesses caused by organic disorders of the nervous system.

Neuropsychiatric disorders are a leading cause of disability and take a tremendous toll on society. In the United States alone, one out of five adults lives with mental illness. The spectrum of mental illnesses is vast, ranging from the extremely rare to more well-known conditions such as depression, anxiety, schizophrenia, ADHD, addiction and sleep disorders. Symptoms and their severity can vary widely from patient to patient, which makes them difficult to physiologically measure. For these reasons, neuropsychiatric disorders are some of the least understood – and some of the most difficult to treat.

“These disorders are a major health issue all over the world, however, therapeutic interventions remain limited,” said NRI/Baylor investigator and child neurologist Dr. Hsiao-Tuan Chao. “There is a growing need to understand the organic factors behind mental illness to facilitate a better understanding of the brain, as well as to develop more effective treatment strategies.”

The symposium opened with a welcome address from Dr. Huda Zoghbi, director of the NRI, and this year’s co-organizer, Dr. Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. The pair stressed the importance of identifying new research paths in order to develop targeted therapies that could not only help treat neuropsychiatric symptoms, but could also help mitigate or eliminate side effects and toxicities that far too many patients experience.

Over the course of the first day, presentations from leading experts addressed hot topics in neuropsychiatry. These included a discussion on how genetic mutations contribute to neuropsychiatric disorders; the involvement of neuronal networks in neuropsychiatric phenotypes; the impact of immune cells on these disorders; and a look into how adaptive deep brain stimulation could potentially help specific conditions. Each session gave way to a 20-minute moderated panel discussion on the topic at hand. This feature of the symposium is unique in that it leads to immediate discussion and active participation among the many different types of stakeholders present.

Following a day of stellar research presentations, the investigators split into three working groups that focused on Molecular Bases of Disease and Human studies, Circuits and Neuromodulation, and Young Investigators. The groups discussed not only everything they had heard over the course of the day, but also their vision for the next 20 years in neuropsychiatry, including the obstacles that currently exist and what is needed to overcome them.

The next morning, key points that had emerged from these discussions were shared with the audience. The working groups identified increased access to resources and funding as a major need. But unanimously, all of the young investigators noted the critical importance of building interdisciplinary, multi-institutional collaborations, with a focus on team science and data sharing.

“Building bridges between various disciplines aids in the identification of important areas of neuropsychiatry that require further investigation and therapeutic development,” said Chao. “Neuropsychiatry itself is an interdisciplinary field, and unraveling the causes for these conditions will require continued interdisciplinary collaborations to accelerate the pace of discovery.”

The proceedings will be published as a white paper in Science Translational Medicine, a leading weekly online journal and one of the event sponsors.

October 23, 2018

The New England Journal of Medicine (NEJM), one of the nation’s most respected peer-reviewed medical journals, has released a new study highlighting the groundbreaking work being done by the Undiagnosed Diseases Network (UDN), an National Institutes of Health-funded research consortium that includes the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital, Baylor College of Medicine, Stanford University and other institutions.

Identifying the genes responsible for rare or unknown disorders using traditional approaches is time-consuming work and can take years, or sometimes even decades. And though genetic sequencing is now a routine part of the care people receive for these types of disorders, many patients are still left without a diagnosis. According to the NEJM study, the collaborative UDN model may already be changing that paradigm.

The study reports that the UDN defined 31 entirely new syndromes, and of 382 completed evaluations, 132 patients received diagnoses, a rate of 35 percent – all in just 20 months. The study also found that of the new diagnoses, 37 percent led to non-therapeutic changes in care, such as narrowing of diagnostic testing, and an amazing 21 percent led to changes in therapies for patients.

“This is a major accomplishment in genomic medicine and a giant step forward for these patients and their families,” said Dr. Huda Zoghbi, director of the NRI.

The UDN was established in 2014 with the mission of providing answers for the millions of patients and their families affected by mysterious and rare conditions, but who, after years of extensive testing, still hadn’t received a diagnosis.

The NRI and Baylor have been at the forefront of discovery in the UDN since its inception, jointly serving as one of seven original clinical sites, where doctors and health care providers, ranging from neurologists, immunologists, nephrologists, endocrinologists and geneticists, come together to help find the cause of participants’ symptoms. Baylor, one of the UDN’s two original sequencing cores, currently acts as the network’s sole DNA sequencing site. The NRI and Baylor were also selected to serve as the UDN’s first Model Organism Screening Center (MOSC), which was spearheaded by NRI investigators Drs. Hugo Bellen, Shinya Yamamoto and Michael Wangler.

“The UDN recognized that the resources we had in place and our high throughput made us the ideal candidate to serve as a MOSC site,” Bellen said. “Because of our success with model organisms and the appreciation physicians have for our work, there will likely be a proliferation of MOSC sites in the future.”

In-depth fruit fly studies at the MOSC have helped physicians and scientists identify genes responsible for rare and undiagnosed disorders, leading to the diagnosis of some of the UDN’s most difficult cases. This collaborative effort, which also includes the University of Oregon, has already directly influenced how clinicians care for patients – patients like Avery Reilly.

At only a few months old, Avery began showing signs of a neurologic condition. She could not sit until age 3 or crawl until age 5, and today she cannot walk or speak. An appointment with Texas Children’s neurologist Dr. Timothy Lotze revealed Avery had poor muscle tone, which was delaying milestones. That initial appointment led to years of doctor visits and countless tests, all of which failed to reveal the cause of Avery’s developmental and speech delays.

Then in 2014, the Reillys heard about the NRI’s involvement with the UDN and submitted Avery’s case. For the first time in years, the family had hope. Using exome sequencing, researchers discovered Avery had a new type of genetic mutation. Then a team at the MOSC, led by Wangler, studied the mutation in a fruit fly model to see how the genes were affected. At long last, the Reillys had a diagnosis. What’s more, the discovery of Avery’s mutation led to a change in her medications, which could help slow the progression of her disease.

“The fact that we are able to help the UDN accelerate science to find actionable changes in therapies is very exciting,” said Zoghbi. “Helping people, and working to solve severe medical problems through basic research, and through unfettered collaboration, is what our work is all about.”

The NEJM study is the first to provide a detailed description of the inner workings of the UDN. It presents an in-depth analysis of the referral and acceptance patterns, diagnoses, impact rates and follow-up scientific investigations of 1,519 cases that were referred to the UDN in the last two years.

As the study points out, the most unique feature, and perhaps the biggest contributor toward UDN’s success, is its model of multi-institutional collaborations. Teams of researchers and physicians from participating institutions all over the nation leverage their multidisciplinary expertise and resources to quickly find specific diagnoses for patients with extremely challenging clinical cases, with no additional cost to the patients.

In addition to the original clinical sites and sequencing cores, the UDN also included a coordinating center as part of its phase I deployment. In 2015, a web-based portal, the UDN Gateway, was launched for patients and families to participate in UDN. The network recently expanded its footprint from seven to 12 clinical sites and also added a central biorepository, a metabolomics core and a new MOSC site.

Though the UDN’s larger focus is currently gene discovery, it’s the work being done at the NRI and Baylor that will set up the network’s next evolution.

“Once a gene is discovered, it’s natural that the focus should shift to finding out what the genes do, what the molecular mechanisms are, if they’re linked to other diseases, or if they can be manipulated with drugs,” Bellen said. “That’s what we’re doing at the NRI and Baylor now, and that will be instrumental in the next phase for the UDN. When that time comes, we’ll be ahead of the curve.”

Learn more about the recent research breakthroughs and patient success stories from the UDN and MOSC.

About the New England Journal of Medicine
For over 200 years, the New England Journal of Medicine has rigorously vetted and compiled the latest medical research in support of physicians and their patients. From the first uses of anesthesia to the most recent cardiology and cancer treatments, the New England Journal of Medicine has helped generations of clinicians enhance their knowledge and improve patient care.

Today, with rigorously peer-reviewed research, topical reviews, interactive clinical content and cases, the New England Journal of Medicine is the trusted source for essential findings in medicine.

October 15, 2018

The Clinical Research Center/Research Resources Office presented the Clinical Research Award for Third Quarter 2018 to Ananth Iyer, Project Manager, Quality Assurance/Quality Control, Department of Pediatrics – Research Resources Office.

This award was established by the Clinical Research Center in collaboration with the Research Resources Office to recognize and honor individual contributions to protecting the best interest of the research subjects and compliance with applicable rules and regulations.

“I joined the Research Resources Office (RRO) in 2014 as a Senior Research Coordinator and am currently in a Quality Assurance (QA) role,” said Iyer. “I take pride in providing support for good quality and compliance in the clinical trials that we undertake. I’m highly motivated by the care and options that clinical research studies provide to patients and never forget that their safety and protection is our top priority. I enjoy the teamwork with which clinical care and research come together in the RRO and I deeply appreciate the RRO for providing me (a lifelong student) with this opportunity.”

September 4, 2018

The Southwest Pediatric Device Consortium (SWPDC), anchored at Texas Children’s Hospital and Baylor College of Medicine, recently received a prestigious P50 grant from the U.S. Food and Drug Administration. The five-year, $6.75 million grant will begin on September 1 and will allow SWPDC to leverage ongoing activities to expand and accelerate the development of much-needed pediatric medical devices. The five principal investigators include Drs. Chester Koh and Henri Justino of Texas Children’s and Baylor, Dr. Balakrishna Haridas of Texas A&M University, Dr. Maria Oden of Rice University, and Dr. Michael Heffernan of Fannin Innovation Studio.

SWPDC supports pediatric device innovators with the goal of addressing the shortage of needed novel medical devices for children, a public health problem that has been acknowledged by the FDA.

“A great need currently exists for medical devices designed specifically for children,” said Koh, founder of SWPDC and lead principal investigator, as well as a pediatric urologist at Texas Children’s and professor of urology, pediatrics and Ob/Gyn at Baylor. “Pediatric device development is challenging, but with this support from the FDA, our consortium will continue to assist pediatric device innovators along all stages of development with the goal of improving our care of pediatric patients.”

The past decade has been a period of growth in adult medical device innovation. Advances in devices for children, however, have lagged far behind. Why the disparity? Economics are partially to blame. The market for pediatric devices is smaller, and thus the return on investment lower. Then there are the clinical and regulatory challenges. Pediatric device projects may need an extended life cycle before they can be approved and exposed to the external market. As a result, pediatric surgeons and pediatricians have had to make do with what’s available, often using retooled adult medical devices, and without adequate testing in children.

“Significant technical (design and manufacturing), preclinical testing, clinical and regulatory testing challenges exist in the field of pediatric devices,” said Haridas, co-founder and co-PI of SWPDC (lead PI at Texas A&M) and professor of practice in biomedical engineering at Texas A&M. “This FDA-funded SWPDC is uniquely positioned to address these challenges across the pediatric device development and clinical translational cycle to deliver significant advances in treatments tailored for pediatric patients.”

Support from the P50 grant will enable SWPDC to provide services in several areas: unmet needs assessment, prototype development, product and technology acceleration services, and business acceleration services. Consortium members will evaluate and support projects, as well as advise innovators throughout the total product life cycle. Based on individual project needs, the consortium will direct investigators to specific resources, collaborators and industry experts, and will coordinate the services offered by its member programs to identify, evaluate and assist pediatric device projects.

SWPDC includes clinical, scientific/engineering, investment, regulatory and academic partners in the Texas Medical Center, the Greater Houston area and the southwestern U.S. Primary partners include Texas A&M University, Rice University, University of Houston and Fannin Innovation Studio, and includes others such as Biotex Inc., Children’s Hospital of San Antonio, Children’s Health in Dallas and Phoenix Children’s Hospital, with additional future sites. SWPDC was selected as one of five national consortia that are addressing the shortage of pediatric devices.

To learn more about the Southwest Pediatric Device Consortium, visit swpdc.org.

August 13, 2018

Thanks to the more than 10 years of dedication and hard work of neonatologists and neonatal nutrition experts at Texas Children’s, Boston Children’s and the University of California at Los Angeles (UCLA) hospitals, premature babies with liver disease now have better access to a potentially lifesaving drug.

On July 27, the FDA approved Omegaven®, an omega-3 fatty-acid-rich lipid solution made from fish oil for use in babies suffering from Parenteral Nutrition Associated Cholestasis (PNAC). For over a decade, Texas Children’s and Boston Children’s have been giving Omegaven® to NICU babies with this disease under compassionate use protocols.

Nearly 20 percent of babies in the NICU develop intestinal failure and are dependent on artificial nutrition (total parenteral nutrition or TPN). Of these infants 25 percent to 50 percent of them develop PNAC, a dreaded complication resulting in long term damage to the liver. Prior to the use of Omegaven®, nearly 50 percent of these babies with PNAC developed liver failure and died, or needed a liver transplant. However, since the use of Omegaven®, 85 percent of infants with PNAC have survived long term, rarely needing a liver transplant.

Being first-hand witnesses to this remarkably improved outcome, neonatologists at Texas Children’s long advocated for the approval of Omegaven. Extensive patient data demonstrating the beneficial effects of Omegaven® on the babies with PNAC from Texas Children’s, Boston Children’s and UCLA formed a crucial part of the new drug approval application submitted to the FDA. Now that Omegaven® is approved by the FDA for use in babies with PNAC, hospitals across the country will have access to it, saving many lives.

“This is a game changer,” said neonatologist Dr. Muralidhar Premkumar. “I am very confident that Omegaven’s approval by the FDA will tremendously improve the outcomes of infants with intestinal failure.”

Program Director of Neonatal Nutrition Dr. Amy Hair agreed and said the approval is “huge, and will most definitely save babies’ lives.”

Over the past decade, liver transplants have decreased nearly 25 percent nationwide in babies with PNAC, mainly as a result of improved multi-disciplinary care of infants with intestinal failure and the use of safer lipid solutions such as Omegaven®. Texas Children’s Newborn Center sees about 25 to 30 babies with the PNAC a year. None of these babies in the past five years have needed a liver transplant.

Charlie and Henry Fitzpatrick were two of those babies. The now 4-year-old twin boys were born prematurely at Texas Children’s Hospital Pavilion for Women and spent six months in the NICU. During their stay, both infants suffered from PNAC and were treated with Omegaven®. Since then, both their liver disease and intestinal failure have resolved. Charlie and Henry are now happy healthy preschoolers.

The twins’ mother, Aly Fitzpatrick, said Omegaven® played a big part in saving her children’s lives and that she is pleased to hear that the FDA approved the drug for use in babies like hers.

“The approval opens up a world of possibilities for these babies,” she said. “Now, more hospitals can embrace this without having to join a research study.”

Because of their experience with the drug, Texas Children’s is uniquely positioned to educate staff at other hospitals about the benefits of Omegaven® and train them on how to use it.

“It gives me great pride and satisfaction that we were part of this successful effort,” Premkumar said. “I would like to thank our dieticians, physicians, NNPs, pharmacists, nurses and of course, the babies and their families who supported us in this endeavor.”

Premkumar added that none of this would have happened if Dr. Steven Abrams and Keli Hawthorne, both former Texas Children’s staff, had not brought this project to the hospital.

July 17, 2018

On July 9, Texas Children’s Hospital and the Angelman Syndrome Foundation celebrated the official opening of the Angelman Syndrome Clinic at Texas Children’s, one of only seven Angelman syndrome-specific clinics in the United States – and the first in Texas.

Several patient families gathered on the 16th floor of Wallace Tower to attend the ribbon cutting ceremony. Debbie Sukin, the daughter of the late Dr. Ralph Feigin, delivered the opening remarks and shared how this new clinic will benefit her 16-year-old son Jacob and so many other children diagnosed with Angelman Syndrome.

“The hardest part of advocating and managing a child with Angelman Syndrome is trying to understand what might be wrong when they aren’t feeling right, looking right or acting right,” Sukin said. “We’re confident that this multidisciplinary clinic here at Texas Children’s will provide all children the expertise and best chance at meeting their maximum potential and provide guidance to ensure the best outcome.”

Occurring in one in 15,000 live births, Angelman syndrome is a neurogenetic disorder often misdiagnosed as autism or cerebral palsy that causes severe neurological impairment. Often times, these patients experience developmental delays, lack of speech, seizures, and walking and balancing disorders.

With the creation of this new clinic established through the generosity of donors and in partnership with the ASF, patients and their families now can access multiple specialists – experts in Angelman syndrome, clinical geneticists, neurologist, psychiatrist, speech language pathologist, genetic counselors and social work – in one setting rather than visiting multiple locations across the nation to manage and treat this disease.

“Thanks to the help of the ASF, we are proud to further our mission of providing very specialized care for patients with Angelman syndrome,” said Chief of Neurology Dr. Gary Clark. “Given the science that’s being developed at the NRI at Texas Children’s in genetics and neurology, we are making great strides in helping these patients.”

The ribbon cutting event also included remarks from Dr. Carlos Bacino, chief of the Angelman Syndrome Clinic, Carrie Rys, assistant vice president, and Eileen Braun, executive director of the Angelman Syndrome Foundation, whose organization donated $50,000 to advance Angelman syndrome research at Texas Children’s.

“Opening this clinic brings us one step closer to our commitment to establish a network of clinics across the country,” Braun said. “We could not be more proud to support Texas Children’s and their remarkable team of professionals in bringing this clinic to life. We look forward to impacting the lives of so many more families.”

Click here to learn more about our Angelman Syndrome Clinic at Texas Children’s.