April 18, 2017

On April 10, more than 600 guests attended the Forum Luncheon at the Marriott Marquis in downtown Houston to meet internationally renowned neurogeneticist Dr. Huda Zoghbi and learn about the remarkable breakthroughs being made at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s Hospital and Baylor College of Medicine.

President and CEO Mark A. Wallace delivered opening remarks including a video documenting the unfolding story of the NRI and how Texas Children’s bold vision of establishing the world’s first basic research institute dedicated to the study of childhood neurological diseases became reality as a result of the hospital’s incredible leadership which he describes as Texas Children’s “secret sauce.”

ABC 13 Anchor Melanie Lawson moderated the one-hour long Q-and-A discussion with Zoghbi, director of the NRI. In addition to learning about Zoghbi’s early career before making the transition to neuroscience research, Zoghbi shared her collaborative vision for the NRI and spotlighted some of the exciting new discoveries emerging from the numerous labs at the NRI.

“To understand a disease, you have to know the root cause,” Zoghbi said. “Once you know the root cause, you can then create an animal model of the disease, dive into the mechanism and find an entry to a therapeutic manipulation. Genetics is one way to find the root cause of disease.”

Since the NRI opened in 2010, Zoghbi highlighted several recent discoveries that have opened new doors for developing therapeutic targets for various neurological diseases:

  • Dr. Benjamin Arenkiel found a small group of cells in the basal forebrain play a major role in the control of appetite. In mouse studies, when these cells are manipulated a certain way, the animal either eats constantly and becomes obese or eats little and loses weight. Arenkiel’s discovery paves the way for developing new therapies to treat obesity and other eating disorders in children and adults.
  • In collaboration with Drs. Juan Botas and Zhandong Liu, NRI researchers have identified a potential new strategy to prevent Alzheimer’s disease. They found that an over accumulation of the protein tau can make the brain vulnerable to degeneration. By developing new drugs to keep tau at levels that are not toxic, this could either prevent or delay the development of Alzheimer’s and other degenerative diseases caused by toxic tau accumulation.
  • Drs. Andrea Ballabio and Marco Sardiello discovered the function of a gene called Transcription Factor EB that helps cells clear up accumulated proteins, which is important for nerve cells to survive. Based on this scientific breakthrough, new clinical trials are underway that will help slow down or stop the progression of disease in patients with Batten disease by improving the clearing function of the brain.
  • Drs. John Swann, Anne Anderson and their team found that there are many molecular and biochemical changes that drive the growth and over-activity of brain cells in epilepsy patients. They were able to define a way to treat these seizures based on biochemical studies in cancer, which has helped to eliminate uncontrollable seizures in children.
    The NRI Forum Luncheon also included inspirational stories from several patient families who were present at the event, and who have benefitted from the life-altering research emerging from the NRI to improve the outcomes and quality of life for patients with a myriad of neurological disorders.

Prior to this event, Texas Children’s Development also hosted a reception to unveil a photography exhibit by Karen Sachar honoring the special needs children in the Greater Houston community. The reception included a short presentation from NRI researcher Dr. Christian Schaaf.

Click here to watch the video of the entire Luncheon Forum program.

Click here to watch specific patient story videos that were featured at the event.

April 4, 2017

The Baylor College of Medicine Department of Pediatrics and Texas Children’s Hospital hosted the 2017 Pediatric Fellows’ Research Symposium on March 21 at the Pavilion for Women Conference Center.

Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute, provided the keynote research presentation, “Protein Levels and Neurological Diseases: Insights and Opportunities.” Besides advancing our understanding of the genetic causes of spinocerebellar ataxia and Rett syndrome, she has been instrumental in other important neurological medical breakthroughs including her recent discovery of how lowering toxic levels of tau in the brain could potentially lead to new therapies to reverse or prevent Alzheimer’s disease.

Dr. Will Parsons, director for the Center for Precision Oncology at Texas Children’s Cancer Center, followed with the keynote scholarship presentation, “Precision Oncology: Deconvoluting One Trainee’s Path from the Bench to the Clinic.”

This year’s research symposium included more than 135 poster presentations from pediatric fellows and included an awards presentation featuring the top four abstracts submitted this year:

  • Bile duct ligation induces ATZ globule clearance in a mouse model Alpha-1 antitrypsin deficiency

Dr. Zahida Khan

  • Respiratory severity score on day of life 15 is higher in premature infants requiring mechanical ventilation at day of life 60

Dr. Matthew Maruna

  • Pharmacogenomic association with neurotoxicity in Hispanic children with acute lymphoblastic leukemia (ALL)

Dr. Claire McClain

  • Inflammatory regulation promotes angiogenesis in chronic renal diseases models

Dr. Xinyi Wang

A fellows’ workshop session was offered as well. Dr. Eric Williams, associate professor of Critical Care at Baylor and Texas Children’s chief medical information officer, led the session on Innovation.

The symposium is an important forum for sharing research results and achievements, as well as for networking and establishing new collaborations. The symposium provides a venue to address topics that may be relevant to the trainee’s career development as they transition to more advanced or faculty positions.

March 29, 2017

Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s and Baylor College of Medicine, is being honored by the Gairdner Foundation with the 2017 Canada Gairdner International Award for seminal discoveries and contributions to biomedical science. This award recognizes some of the most significant medical discoveries from around the world.

Zoghbi, who also is professor and Howard Hughes Medical Institute Investigator at Baylor, is one of five individuals given this award. She is being recognized for her work surrounding the discovery of the gene responsible for Rett syndrome.

After years of treating patients, Zoghbi began to focus on finding the genetic causes of the disease, which strikes after a year of normal development and presents with developmental regression, social withdrawal, loss of hand use and compulsive wringing of the hands, seizures and a variety of neurobehavioral symptoms.

Zoghbi identified that mutations in MECP2 are the cause of Rett syndrome, revealing the importance of MeCP2 for the function of various neuronal subtypes. Her work showed just how sensitive the brain is to the levels of MeCP2 and that doubling MeCP2 levels causes progressive neurological deficits. This disorder is now recognized as MECP2 Duplication Syndrome in humans.

Her recent work showed the symptoms of adult mice modeling the duplication disorder can be reversed using antisense oligonucleotides that normalize MeCP2 levels.

The discovery of the Rett syndrome gene provided a straightforward diagnostic genetic test, allowing early and accurate diagnosis of the syndrome. It also revealed that mutations in MECP2 also can cause a host of other neuropsychiatric features ranging from autism to juvenile onset schizophrenia. Further, it provided evidence that an autism spectrum disorder or an intellectual disability disorder can be genetic even if it is not inherited.

Her discovery opened up a new area of research on the role of epigenetics in neuropsychiatric phenotypes. Her use of an antisense oligonucleotide to lower MECP2 levels provides a potential therapeutic strategy for the MECP2 duplication syndrome and inspires similar studies for other duplication disorders.

Zoghbi will be presented her award at a gala in Toronto on Thursday, October 26. Each award carries an honorarium of $100,000 to support continued research.

January 17, 2017

11817NEURO640“My 5-year old daughter is such a cute, vivacious little girl who lights up a room,” said mom Evonia Dunlap. “When Bristol was born, she was perfectly healthy but by the time she was 3 months old, she was failing to reach her milestones and began showing worrisome symptoms.”

Bristol could not lift her head up or sit upright, her body was unusually floppy and flexible, and her left eye began turning inward, even though her vision was fine. As Bristol grew older, she was slow to crawl, stand and walk, and had difficulties in chewing, swallowing and talking.

“My daughter seemed to be very resistant to physical pain,” Dunlap said. “She would never cry when she fell down, bumped into things or received her vaccine shots, which was very, very unusual.”

Bristol was diagnosed with congenital hypotonia, a symptom that can be caused by various neurological or non-neurological conditions, which explained the poor muscle tone throughout her body. She had corrective eye surgery and Dunlap credits the physical, occupational and speech therapies with helping her daughter sit, walk and communicate.

But there was one thing Dunlap wanted to know. What caused Bristol to develop hypotonia?

After consulting many specialists who performed a battery of diagnostic tests and assessments for cerebral palsy, Down syndrome, autism, muscular dystrophy and many others, the results came back negative. Whole exome sequencing, a test that looks for misspellings in a gene, was inconclusive.

After five years searching for answers, Dunlap’s medical odyssey ended at Texas Children’s when Bristol was referred to neurologist Dr. Hsiao-Tuan Chao and geneticist Dr. Michael Wangler, physician scientists in Dr. Hugo Bellen’s lab at the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s.

Bellen’s team is an important part of the Undiagnosed Disease Project, a national network established by the National Institutes of Health. Through this initiative, they came to know of a 7-year-old boy who had symptoms remarkably similar to Bristol’s and carried a point mutation in the Early B-Cell Factor 3 (EBF3) gene.

After closely re-examining Bristol’s exome sequencing results, they found she also carried the exact same mutation that produces defective EBF3 protein. Since EBF3 is a master regulator of hundreds of other genes, even the tiniest alteration in its function could potentially cause widespread damage to the developing nervous system and muscles.

The team also learned of another little girl at NYU’s Langone Medical Center who had a similar medical history and was found to carry the exact same EBF3 mutation. The NRI team thought this was truly remarkable and postulated that variation in EBF3 could be the possible link between these two children and Bristol.

The team extensively studied the fruit fly and mammalian versions of EBF3 and concluded the point mutation in EBF3 was indeed the culprit behind the symptoms exhibited by Bristol and the others. In the last six months alone, at least 20 patients around the world have been found to carry the damaging mutations in the EBF3 gene.

While the journey to find a cure for this condition has just begun, Dunlap is happy to finally have some answers.

“Thanks to this study, physicians around the world will now have some understanding of this condition, which we anticipate, will help to diagnose many children in the future,” Dunlap said. “I fervently hope I can now connect with other families of children with EBF3-related disorders so we can learn from and support each other.”

December 5, 2016

12516zoghbi640On Sunday, December 4, Texas Children’s and Baylor College of Medicine’s pioneering neuroscientist Dr. Huda Zoghbi was honored with the Breakthrough Prize in the field of Life Sciences during a star-studded ceremony in San Francisco’s Silicon Valley.

Awarded annually to the world’s top scientists in fundamental physics, mathematics and the life sciences, the Breakthrough Prize is considered Silicon Valley’s most significant science prize for what they cite as paradigm-shifting research. The Prize was founded by Sergey Brin (Google), Anne Wojcicki (23andMe), Mark Zuckerberg (Facebook), Priscilla Chan (Chan Zuckerberg Initiatives), Yuri Milner (DST Global) and Julia Milner.

Presented during a live broadcast on the National Geographic Channel, Zoghbi was recognized for her discoveries of the genetic causes and biochemical mechanisms of spinocerebellar ataxia, a neurodegenerative disorder affecting balance and coordination, and Rett syndrome, a genetic neurological disease characterized by the loss of motor skills, speech and other cognitive abilities affecting girls one or two years after birth. Prior to Zoghbi’s pioneering work in neuroscience, little was understood about the causes of these diseases, let alone how to potentially treat or cure them.

As one of the world’s leading neurogeneticists, Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children’s and Baylor, has been instrumental in other important medical breakthroughs in neurological disease research including her most recent discovery of how lowering toxic levels of tau in the brain could potentially lead to new therapies to reverse or prevent Alzheimer’s disease.

“We are tremendously proud of the transformational work Dr. Zoghbi and her team are doing at the NRI. The numerous discoveries coming from Texas Children’s and Baylor will have an immeasurable impact on so many of our families suffering from unexplainable neurological diseases,” said Texas Children’s President and CEO Mark A. Wallace. “Please join me in congratulating Dr. Zoghbi for this well-deserved and prestigious global recognition.”

Zoghbi plans to donate the majority of her $3-million Breakthrough Prize to support education and research initiatives. She wishes to recognize the institutions that impacted her career including Texas Children’s and Baylor. The gifts will help advance genetic and neuroscience research.

Zoghbi thanked her supporters with the following acceptance speech: “As a young doctor, I found it heartbreaking to watch my patients, young and old, lose their lives to neurological diseases. I turned to research for answers, and today, together with collaborators and trainees, we are charting new paths towards viable therapies. It’s thrilling to see we are beginning to understand the language of life and translate it to help mankind. I feel fortunate to have had my career nurtured by two of the finest institutions, Baylor College of Medicine and Texas Children’s Hospital and to have the support of the Howard Hughes Medical Institute. I thank my husband William and our children, Roula and Anthony, for their unwavering support, and they share this honor with me today.”

Click here to learn more about the ceremony and this award including a feature story on Zoghbi from the Houston Chronicle. FOX will air a one-hour version of the ceremony on Sunday, December 18, at 6 p.m.

In addition to this accolade, Zoghbi has earned dozens of honors and awards, including most recently the 2016 Shaw Prize in Medicine and the 2016 Jessie Stevenson Kovalenko Medal for her research.

November 15, 2016

111616epilepsyinside640Imagine being a parent of a child who has uncontrollable seizures. After numerous doctor visits and four failed medication attempts, the cause of your child’s seizures remains a mystery. That was the grim reality Mallory Hansen and her husband, Craig, faced after their son’s epilepsy diagnosis.

“When Noah was 10 weeks old, we noticed he was not acting normally,” Hansen said. “We learned he was experiencing infantile spasms. He would have anywhere from 10 to 30 seizures a day, and with each occurrence, he experienced 30 to 100 epileptic twitches.”

Despite being diagnosed with epilepsy at four months old, Noah underwent numerous tests including MRIs, blood work, EEGs, seeing a neurologist and a genetic doctor to pinpoint the cause of his seizures, but still no answers. When their son was two years old, the Hansens relocated to Houston and Noah’s medical files were transferred to Texas Children’s Hospital. It was there that the family finally got the answers to their son’s perplexing medical condition.

“The neurology team at Texas Children’s performed more tests including nuclear medicine, MRIs and EEGs in their Epilepsy Monitoring Unit which meant Noah had to stay in the hospital for multiple days,” Hansen said. “It was after an MRI that the neurologist discovered the reason behind Noah’s seizures and epilepsy.”

At the age of two, Noah finally had a diagnosis: His right occipital lobe had brain tissue that did not develop correctly as an embryo which was causing his seizures.

Since previous medications didn’t stop Noah’s seizures, the only option remaining was brain surgery. During the first phase of surgery, an 8×6 grid was placed on the top of his brain like a mini EEG and electrodes were inserted to show the depth of Noah’s seizures. After two days of recording his seizures, Texas Children’s neurosurgeons had enough information to perform the resection surgery where they removed the bad tissue from Noah’s right occipital lobe.

Following two 12-hours operations, Noah has made a miraculous recovery with promising outcomes.

“Since his surgery in July 2014, Noah has not had a single seizure,” Hansen said. “Since May 2016, he’s been off all three of his seizure medications. Thanks to Texas Children’s, the entire epilepsy team, emergency unit, neurosurgeons, critical care team and all the staff we encountered, we are forever grateful.”

Like the Hansens, patients families from across the country come to Texas Children’s because of our neuroscience team’s multidisciplinary care and expertise in caring for the most difficult to treat neurological disorders.

Ranked No. 2 nationally in neurology and neurosurgery by U.S. News & World Report, Texas Children’s neurosurgery program is among the largest and most experienced pediatric neurosurgery units in the U.S., performing more than 950 surgeries annually for a broad range of pediatric neurosurgical disorders.

For more information about Texas Children’s Neuroscience Center, click here.

November 1, 2016

11216nribrain640A new study published in the journal Neuron found that taking a pill that prevents the accumulation of toxic molecules in the brain might someday help prevent or delay Alzheimer’s disease.

According to researchers at Texas Children’s Hospital, Baylor College of Medicine and Johns Hopkins University School of Medicine, the study took a three-pronged approach to help subdue early events that occur in the brain long before symptoms of Alzheimer’s disease are evident.

“Common diseases like Parkinson’s, Alzheimer’s and dementia are caused in part by abnormal accumulation of certain proteins in the brain,” said senior author Dr. Huda Zoghbi, director of the Jan and Duncan Neurological Research Institute at Texas Children’s. “Some proteins become toxic when they accumulate and they make the brain vulnerable to degeneration.”

Tau is one of those proteins involved in Alzheimer’s disease and dementia. When tau accumulates as the person ages, it increases the vulnerability of the brain to developing Alzheimer’s.

“Scientists in the field have been focusing mostly on the final stages of Alzheimer’s disease,” said first author Dr. Cristian Lasagna-Reeves, postdoctoral fellow in the Zoghbi lab. “Here we tried to find clues about what is happening at the very early stages of the illness, before clinical irreversible symptoms appear, with the intention of preventing or reducing those early events that lead to devastating changes in the brain decades later.”

To find out which enzymes affected tau accumulation, the scientists inhibited about 600 enzymes called kinases one by one and found one, called Nuak1, whose inhibition resulted in reduced levels of tau.

By confirming this discovery in three different experiments – in fruit flies, mice and human cells – the researchers said the next step is to develop drugs that will block the production of Nuak1.

“If we can find drugs that can keep tau at levels that are not toxic for the brain, we would be able to prevent or delay the development of Alzheimer’s and other diseases caused in part by toxic tau accumulation,” Zoghbi said.

Click here to read the joint Baylor and Texas Children’s news release for more details on this study.