April 14, 2020

The development of a COVID-19 vaccine is the greatest medical need of our generation—and Texas Children’s is on the front lines.

Drs. Peter Hotez and Maria Elena Bottazzi, who co-direct Texas Children’s Center for Vaccine Development, are rapidly advancing their work on vaccines that will protect against COVID-19 and other coronaviruses.

“Without a vaccine, we’re using 14th-century methods of prevention—that’s what quarantining and social distancing are, and we have to use these methods, “ Hotez said. “But vaccines have always been our best and most powerful front-line public health defense against widespread infection, and they are the answer—now and in the future—for COVID-19 and other coronaviruses.”

Most people aren’t aware that there is an entire family of coronaviruses. The one that has ignited our global pandemic is SARS-CoV-2, the virus that causes COVID-19. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are two others that have emerged in recent years.

Drs. Hotez and Bottazzi, along with their teams, have already developed recombinant protein-based vaccines against SARS and MERS. One of them is ready to be tested in humans; the other is ready for scaled-up production. We are now using our extensive expertise with these related viruses to develop a vaccine for COVID-19 and quickly move it into the clinic.

In a recent interview on the nationally syndicated health show “Dr. Oz”, Dr. Hotez shared his thoughts on COVID-19 and what he feels the future will bring. You can view part one and part two of the interview.

To learn more about the work taking place at Texas Children’s Center for Vaccine Development visit TexasChildrensVaccines.org.

March 2, 2020

Texas Children’s Neurosciences Program is all about improving patient outcomes. Every day, our team of neurologists, neurosurgeons, geneticists, physician-scientists and researchers are working together tirelessly to pioneer innovative therapies to improve the lives of children with neurological disorders.

On February 21, neuroscience leadership at Texas Children’s together with faculty and staff convened for the inaugural Neurosciences Retreat at the Jan and Dan Duncan Neurological Research Institute (NRI). This informative and engaging event provided our multidisciplinary team of neurologists, neurosurgeons, clinicians, researchers, behavioral health experts, and more the opportunity to reflect on past successes, discuss areas of possible improvement, identify transformative goals and actively plan for the future.

After welcome remarks from Executive Vice President Dan DiPrisco, the retreat began with a moderated panel discussion with two patient families who shared their inspiring stories that brought them to Texas Children’s Hospital. One of the guests was Debbie Sukin, the daughter of the late Dr. Ralph D. Feigin.

Sukin’s two sons, 18-year-old Jacob and 15-year-old Eli, were born with neurological challenges. Jacob was diagnosed with Angelman’s syndrome and Eli was diagnosed with a very rare neurological disorder caused by a CASK gene mutation diagnosed through genome DNA sequencing at Texas Children’s Hospital and Baylor College of Medicine.

“Texas Children’s holds a very special place in my family’s heart,” Sukin said. “We always knew about the hospital’s focus on clinical care and research, and didn’t quite know at the time that it would be so beneficial and important to our family. We are very much involved, on both the basic science and clinical sides, and the multidisciplinary components that are necessary to care for a child with neurological issues.”

The Sukin family’s journey, like so many other patient family stories shared at the retreat, highlight our clinical and research partners’ collaborative efforts in advancing neuroscience research, ultimately leading to the development of novel treatments and discovery of cures for neurological disorders.

“We’re always striving to do things better, and I think this retreat is one step towards getting us there,” said Texas Children’s Chief of Neurosurgery Dr. Howard Weiner. “Everyone here is ready to embrace a new idea if it’s going to advance the field forward. The key to our success is the ability for everyone – in Neurosurgery and our amazing colleagues in Neurology and the NRI – to work together for our patients.”

Weiner, along with Dr. Gary Clark, chief of Neurology and Developmental Neuroscience, and Dr. Huda Zoghbi, director of the NRI, participated in a panel discussion that highlighted the organization’s bench-to-bedside achievements in neuroscience research and neurological care over the last 20 years, and outlined collaborative opportunities to accelerate innovation and research to improve patient outcomes.

“We’re entering the renaissance of neuroscience in pediatrics,” Clark said. “Neurology and neurosurgery are not the same programs they were five or 10 years ago. Neurological diseases that we thought for years were not treatable, have become approachable with new DNA therapies, enzyme replacement therapy to treat lysosomal disorders, and minimally-invasive surgical approaches like laser ablation, that was pioneered at Texas Children’s, and has yielded successful outcomes for treating epileptic seizures.”

The panel also discussed strategies to ensure a seamless flow from bench to bedside, that will help researchers accelerate the discovery behind the causes of neurological diseases so that effective therapeutic interventions can be developed to improve the quality of life and outcomes for patients.

“At the NRI, our teams have identified the causes of about 66 different neurological disorders, some degenerative, others developmental or psychiatric, and have identified the path for therapeutics,” Zoghbi said. “Together, with our collaborators and trainees, we are charting new paths towards viable therapies that will have an immeasurable impact on families suffering from unexplainable neurological diseases.”

After the panel discussions, attendees split up into pre-selected breakout groups. The teams chose their groups based on the topic, and were tasked with helping to establish neuroscience goals and collectively chart the path for treatments, discoveries and cures to be realized over the next five years

The breakout groups facilitated lively discussion and engagement around these topics:

  • Operational Excellence: Facilitating support for clinical care and research
  • Translating Discoveries to Therapies: Overcoming barriers in order to accelerate the translation of research discoveries into effective patient care and better outcomes.
  • Population Health: Strategizing on how to deliver better care to the large population of people with neurological diseases in Texas by preparing and empowering pediatricians to handle straightforward simple cases so Texas Children’s experts have band width to see more complex cases promptly.
  • Educating for the Future: Training the next generation of physicians, physician-scientists and scientists who will care for patients, enroll them in studies, push the research forward to discover new paths for interventions.
  • Research Funding: Increasing NIH funding to support the basic, clinical and training missions and to advance the agenda of discovery and therapeutics development.

“One of our goals coming into this retreat was to simply facilitate discussions,” said Senior Vice President Matthew Girotto. “We have world renowned clinical and research teams that, too often, do not connect with each other. By simply bringing everyone together, we were able to uncover several opportunities that could not only help accelerate discovery to improve patient care but also increase our collaboration with Texas Children’s Pediatrics in addressing many of the common neurological needs of children.”

November 18, 2019

During the final week of October, Texas Children’s Hospital hosted visitors from around the world for a very special Rett Syndrome Symposium and Workshop.

The two-day event was momentous for many reasons. It was the inaugural meeting held in the stunning new Auditorium and Conference Center at the Jan and Dan Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital. It fortuitously coincided with Rett Syndrome Awareness Month. And the symposium also marked the 20th anniversary of the discovery of the underlying cause of Rett syndrome. In 2000, NRI director Dr. Huda Zoghbi’s research team made the pioneering discovery that loss-of-function mutations in methyl-CpG binding protein, MECP2, were the underlying cause of Rett syndrome.

Rett syndrome is a rare neurological disorder that primarily affects young girls between 6 months and 2 years of age. The children appear to hit normal developmental milestones until, inexplicably, their motor, cognitive and social skills start to rapidly deteriorate. Most patients develop autistic features, breathing difficulties, dementia, growth abnormalities, epilepsy and scoliosis.

The symposium opened with a warm welcome from co-organizers Dr. Adrian Bird – Buchanan Professor of Genetics and Welcome Trust Center for Cell biology at the University of Edinburgh, UK – and Zoghbi, who is also a professor at Baylor College of Medicine and Howard Hughes Medical Institute investigator.

“The purpose of this event was to bring together researchers who work on Rett syndrome and leaders from related areas of neuroscience working in academia, industry and government, to think deeply and spark new ideas,” said Zoghbi. “The hope is that out of the work and discussions that happened here, in five years, when we’re marking the 25th anniversary of the gene discovery of Rett syndrome, we’ll also be celebrating new treatments for people with Rett syndrome.”

The international symposium was sponsored by Rettsyndrome.org (formerly the International Rett Syndrome Foundation) and the Rett Syndrome Research Trust. The multidisciplinary group of attendees included scientists, physicians, members of the lay public, and representatives from the National Institutes of Health, the pharmaceutical industry, and several foundations, all brought together to look at Rett syndrome with a fresh, new perspective.

On the first day of the symposium, presentation topics ranged from clinical observations of MECP2 disorders like Rett and MECP2 duplication syndrome to pathogenesis (progression or development) of Rett syndrome, to discussions on neuronal circuit alterations and therapeutics. Texas Children’s pediatric neurologist Dr. Bernhard Suter spoke about MECP2 duplication syndrome, which typically affects male patients and causes symptoms such as hypotonia, motor delays, intellectual disabilities, gastrointestinal issues and epilepsy.

Following a day of stellar research presentations, the investigators split into three working groups that focused on Molecular Pathogenesis, Therapeutic Approaches and Young Investigators. The groups discussed the information presented over the course of the day and their vision for the future of Rett syndrome research. This included the systemic and technical challenges that currently exist, and the group brainstormed ways to overcome those. The next morning, key points from these discussions were shared with the audience.

  • Rett syndrome is a particularly challenging disorder to correct. The levels of MECP2 protein in the neurons need to be precisely regulated because too much MECP2 protein causes a different neurological condition, the MECP2 duplication syndrome. Despite these challenges, research in Rett syndrome is advancing at a rapid pace, having moved from gene discovery to promising clinical trials in under 20 years.
  • Gene therapy offers exciting opportunities to develop treatment for Rett syndrome and is an area of active research. However, there are challenges to overcome including controlling the level and distribution of the delivered gene.
  • While the ultimate long-term goal of researchers is to find a lasting cure using gene therapy, clinicians in the audience weighed in on the benefits of also developing short-term strategies to treat specific behavioral or motor issues and/or how to delay the age of symptom onset. This would be a huge step forward for patients, their families and caregivers who cope with this debilitating condition on a daily basis. Participants in the discussion also drew parallels to the field of breast cancer, where non-targeted treatment modalities serve as the workhorses to treat the majority of patients.
  • There is a dire need to develop early screening/diagnostic methods for Rett syndrome among newborns. Early diagnosis, in combination with specialized therapies – such as neuromodulation physical therapy, speech therapy or psychotherapy may provide maximal improvements in the quality of life of the patients.
  • Building collaborations between academia and industry, with a focus on multidisciplinary team science and data-sharing, is critical to facilitate the development of superior reagents (i.e., better viral vectors for gene therapy), biomarkers (i.e., meaningful measures of clinical outcomes) and therapies. Moreover, there was a general agreement that close partnerships between various key stakeholders, such as scientists, physicians, pharma/biotech industry, families, caregivers and advocacy groups, are crucial for developing effective therapies.

Learn more about Texas Children’s research efforts at the Jan and Dan Duncan Neurological Research Institute and world-class clinical expertise provided at the Rett Center.

October 15, 2019

The Clinical Research Center/Research Resources Office presented the Clinical Research Award for third Quarter 2019 to Ann McMeans, Clinical Research Center at Texas Children’s Hospital.

The 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.

Ann McMeans began work as a pediatric dietitian in 1992 at Texas Children’s Hospital. In 1998, she transitioned to the Clinical Research Center (CRC) at Texas Children’s Hospital and has worked for more than 21 years as a research dietitian. McMeans also manages the CRC database, the Scientific Advisory Committee meetings and the nutrition studies in the Children’s Nutrition Research Center Metabolic Research Unit. She was President of the National Association for Research Nutrition from May 2018-May 2019.

Her more recent research projects include being an unblinded team member for various peanut food allergy studies and various studies focusing on IBS in the pediatric population.

September 17, 2019

As one of the best pediatric cancer centers in the nation, experts at Texas Children’s Cancer Center are on the forefront of cutting-edge basic, translational and clinical research. The center’s world-renowned faculty have pioneered many of the now standard protocols for treating and curing children with cancer.

Scientists and clinical experts at the center are conducting more than 250 clinical trials – more than the majority of pediatric cancer centers in the nation. In addition, the center’s Developmental Therapeutics Program and its Cell and Gene Therapy Program have been leaders in the study of novel agents and immunotherapies, respectively, for the treatment of childhood cancer.

“Our physicians employ evidence-based guidelines and the most advanced clinical trials in the delivery of oncology care,” said Cancer Center Director Dr. Susan Blaney. “Our vast expertise in the development of new therapeutics means our patients have access to the most advanced and innovative therapies.”

Dr. Andras Heczey, one of the Cancer Center’s physician scientists and a member of the newly-formed Sky High Immunotherapy Center, is working with colleagues in his laboratory to develop novel treatments for children with solid tumors. His work is a prime example of what the Cancer Center is doing to advance treatments and ultimately find a cure for a disease that remains the leading cause of non-accidental death in children.

In honor of National Childhood Cancer Awareness Month, we interviewed Heczey about his research and why he thinks such work is so important to enhanced patient care.

What is the focus of your research?
My research focuses on redirecting the normal immune system to attack cancer cells. T cells are a type of white blood cell that participate in the immune response. I am using genetically engineered T cells to treat liver tumors in children and Natural Killer T (NK-T) cells to treat neuroblastoma, a childhood tumor that most commonly involves the adrenal gland.

How exactly does this work?
We take patients’ white blood cells from a simple blood draw, modify them in the test tube to recognize and kill tumor cells, and then re-infuse these genetically engineered (modified) cells into the patient’s blood stream. The idea is that we train the immune system to kill the cancer cells. In patients with neuroblastoma, we modify Natural Killer T cells to express a protein called chimeric antigen receptor (CAR for short) that targets GD2, a molecule on tumor cells but not on normal tissues. When the Natural Killer T cells arrive at the neuroblastoma tissue, they recognize the GD2 molecule and kill the cancer cells. In liver cancer patients, we are using a similar strategy using T cells that express CAR targeting a molecule called Glypican-3, which is primarily expresses on liver cancer cells.

Have you used these treatments in children at Texas Children’s?
Last summer, we started our first human clinical study in children who have relapsed or have refractory high-risk neuroblastoma. So far, three children have been treated. The results we have observed thus far are very promising. We also have started our first human clinical study in children with relapsed or refractory liver cancer. The first patient was recently treated and we are eagerly waiting for the results.

What else are you studying in your laboratory?
In addition to developing strategies to kill the tumor cell, we are also closely studying the tumor environment. We know that when genetically engineered cells enter the tumor, the cancer cells and other cells within the tumor will fight back. We don’t really know how this happens. We have some ideas, but we and others in the field are closely evaluating what happens in human tumors after the engineered cells are infused. This is really important because we want to make sure our cell therapies are effective and that the responses are sustained and the patients are cured. Ultimately, we’ll also need to develop techniques to engineer the cells inside the body. Right now, we have to grow and test the cells before infusing them into the patient. This typically takes four to six weeks, depending on the product and how many cells needed to be manufactured. A patient cannot always wait that long. In the future, we envision strategies where a patient’s immune cells are engineered inside their body to quickly redirect them against the growing tumor cells.

Are you encouraged by what you are finding?
Yes, I am very encouraged. We are getting closer each and every day to finding a cure for some forms of childhood cancer.

Click here to view a preview of the next installment of “This is Cancer: Reflections from our patients.” This installment focuses on Tajah, who was diagnosed with osteosarcoma after visiting Texas Children’s Emergency Center with intense knee pain. The 13-year-old had to have her knee and femur removed. Surgeons replaced them with a metal extendable one, which will prevent her from undergoing several additional surgeries as she grows. The “This is Cancer” series documents the journeys of several families receiving care at Texas Children’s Cancer and Hematology Center. Their stories illustrate in intimate detail what they’re experiencing and how to better support them. Click here to learn more.

September 16, 2019

The Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital recently hosted the first-ever family conference for EBF3-HADD (Hypotonia, ataxia and delayed development) syndrome (HADDS). Medical residents, genetics counseling students and research scientists joined more than 20 families from across North America that attended in person and 13 families that participated via live-streaming services from countries around the world – including Ireland and Australia – making it a truly international event.

The conference was organized by the EBF3-HADDS Foundation, a nonprofit organization created in 2018 by families to promote awareness, research and support for this genetic syndrome. The foundation was co-founded by Ashley LeMaire and her husband, Mark. After one of their children was diagnosed with HADDS in 2016, the LeMaires started a Facebook group for HADDS families. In just two years, that group has grown into an international community and was the impetus behind the foundation’s creation.

“Our HADDS community is a motivated and talented group of families dedicated to supporting research, education and advocacy efforts for HADDS patients, and we support each other on this journey,” said LeMaire, who is a clinical neuropsychologist at the Menninger Clinic, assistant professor of Psychiatry & Behavioral Sciences at Baylor College of Medicine, and also board member of the EBF3-HADDS Foundation. “There is still much to learn about HADDS, but when you have such a dedicated team of physicians and researchers collaborating with families to learn about the condition and provide needed support, it fosters so much hope for our families.”

During the conference, guests attended presentations on a variety of HADDS-related topics given by NRI researchers Drs. Hsiao-Tuan Chao and Michael Wangler; pediatric urologist Dr. Irina Stanasel, a former Texas Children’s fellow; Texas Children’s genetic counselor Pilar Magoulas; and Geraldine Bliss, research director of the Phelan-McDermid Foundation. Additionally, Chao and Wangler offered clinical evaluations for patients, and attendees were also able to tour research labs and facilities at the NRI, where one of the first genetic discoveries for HADDS was made in 2016, and the first lab (Chao’s) devoted to understanding the biology of this disorder.

A search for answers

If you’ve never heard of HADDS, there’s a good reason. The rare genetic disorder, caused by a mutation in the EBF3 gene, was only discovered in 2016 by Chao and Wangler when they were training in NRI investigator Dr. Hugo Bellen’s lab, in collaboration with colleagues at the Undiagnosed Diseases Network (UDN) and New York University Langone Health.

The UDN had been stumped by a case in which a child exhibited symptoms including impaired speech and cognition, low muscle tone, balance and gait issues, reduced ability to feel physical pain, and an inability to show facial emotional expressions. Though earlier DNA sequencing had yielded a few candidate genes, there wasn’t a significant patient cohort or research to help determine which gene was responsible for the symptoms.

Researchers selected EBF3 as the most likely candidate gene. Chao then used fruit flies to mimic mutations to better understand EBF3’s role, and within a few months three patients were found who presented with similar symptoms and similar mutations in the EBF3 gene.

As result of those efforts, more than 200 patients with HADDS have been identified to date.

“The gene discovery of EBF3 illustrates the ‘Power of One’ in medicine and biomedical research, how a single patient with an undiagnosed disorder – a ‘medical mystery’ – can lead to the discovery of a gene responsible for a previously unknown disorder,” Chao said. “This becomes the starting point to develop the diagnostic tests and therapies that can transform the lives of many patients and their families.”

Since 2017 Chao and Wangler have offered monthly clinical evaluations for HADDS patients at Texas Children’s and have now seen the largest number of such patients at any single institution worldwide. They are also enrolling patients in a study to better understand the condition and to help translate research into potential clinical interventions in the future.

The conference was a testament to the power of teamwork and collaboration in research, and also shows how dedicated parents and volunteers from across the globe can work together to build a community of support.

September 10, 2019

The Meyer Center for Developmental Pediatrics at Texas Children’s Hospital, Baylor College of Medicine and the Spina Bifida Association recently hosted the Houston Spina Bifida Education Day for patients, families and caregivers. Held at Houston Methodist Hospital, the event showcased newly established, evidence-based national guidelines for the care of individuals living with spina bifida. This is the first time the guidelines, written in part by Texas Children’s and Baylor clinicians and researchers, were shared with such a broad audience.

More than 100 people from across Texas and other states as far as Florida and Indiana attended the event. In addition to unveiling the new guidelines, experts from Texas Children’s presented talks covering a range of health issues faced by individuals living with spina bifida from infancy to adulthood. There also were presentations on related topics such as care coordination, emotional wellness, skin, and bowel-management tips specifically geared toward this group of families.

“Usually, clinical care guidelines are widely shared and disseminated among medical practitioners, not so much the lay public, so this conference not only provided professional guidance, but also much needed peer-to-peer advice,” said Dr. Ellen Fremion, a physician in the Spina Bifida Program at Texas Children’s and one of the organizers of the event. “Moreover, the heartfelt appreciation and deep emotional reactions from the families who attended this conference exemplifies how crucial it is to empower patients, families and caregivers with this kind of information, so they are better equipped to care for themselves and their family members.”

Spina bifida (meaning “split bone”) is the most common permanently disabling birth defect seen among newborns in the United States. It is a type of neural tube defect that occurs when a baby’s neural tube fails to develop or close properly. The symptoms of this condition range from mild to severe, depending on where the spinal cord is affected. Myelomeningocele is the most severe form of spina bifida in which parts of the spinal cord and nerves come through the open part of the spine. This leads to several related problems such as loss of feeling in areas below the opening, weakness or paralysis of the feet or legs, problems with bladder and bowel control. Some affected individuals have additional neurological complications, including a buildup of excess fluid around the brain (hydrocephalus) and diverse cognitive challenges. Multiple environmental (such as folic acid deficiency) and genetic factors are thought to cause this complex condition, although the exact causes are still unclear.

The Meyer Center’s Spina Bifida Program at Texas Children’s is a multidisciplinary program that includes several specialty services: neurosurgery, developmental pediatrics, urology, orthopedics, and physical medicine and rehabilitation. Experts from these specialties offer prenatal evaluations and follow patients from in utero to adulthood.

In 2011, Texas Children’s was among the first centers to perform open fetal surgery to treat spina bifida. Using this procedure, the defect in the fetal spine is accessed and repaired through an incision across the mother’s uterus (womb), and has since been the standard of care for spina bifida. In 2014, Texas Children’s Fetal Center pioneered a novel minimally-invasive fetoscopic procedure, in which the spinal defect is repaired through tiny incisions in the uterus using a small camera. This offers the same improved outcomes as the open fetal surgery but comes with additional benefits and reduced health risks.

“Despite recent advances of in utero repair procedures, surgery is not suitable for all patients and cannot be considered a cure,” said Dr. Jonathan Castillo, clinical director of the Spina Bifida Program at Texas Children’s. “Additionally, these surgeries may not reverse all the function or correct all related impairments. Also, these procedures are specific to myelomeningocele and may not help patients with other forms of spina bifida. Therefore, a deeper understanding of the etiology and biology of this condition is crucial to develop better treatment approaches in spina bifida care.”

In addition to providing cutting-edge clinical services, physicians and researchers at Texas Children’s Spina Bifida Program also are engaged in comprehensive, multidisciplinary research initiatives to find newer and safer medical and surgical interventions that can improve the quality of life for these individuals.

In 2014, a multidisciplinary team of experts at Texas Children’s Spina Bifida Program led by Drs. Heidi Castillo, Jonathan Castillo and Duong Tu, received a federal grant from the U.S. Centers for Disease Control and Prevention (CDC) to develop national standards in spina bifida care at the population level. Texas Children’s was the only funded hospital in Texas to be included in this effort, and, along with Baylor, was among the first institutions in the state to participate in the CDC’s National Spina Bifida Registry that collects medical data from this population to improve outcomes.

“Receiving that grant from the CDC and joining the registry gave us an amazing opportunity to participate in a nation-wide effort to develop better outcomes, interventions and standards of care for individuals with spina bifida,” Castillo said. “Since we are one of the major referral sites for spina bifida in the state of Texas, our team provides the entire spectrum of care to pediatric patients – from prenatal diagnosis, surgical interventions and postnatal care until adulthood – for myriad health issues related to spina bifida. This gives our team access to a wide demographic of participants and allows us to conduct unique in-depth studies and comparisons of the outcome measures of current interventions.”

“These studies have led to important findings that are reflected in the recent clinical care guidelines, and have revealed consistent disparities in the outcomes based on patient’s socioeconomic conditions and ethnicity, a novel observation that is currently under further investigation,” Castillo said. “Our team is excited that recently the CDC granted an extension of this grant for five more years, so we can continue to be at the forefront of comprehensive clinical care and research initiatives that will improve the lives of individuals living with spina bifida.”