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.

October 11, 2016

4115Drzoghbi640The Shaw Prize Foundation awarded the 2016 Shaw Prize in Life Science and Medicine to pioneering neuroscientist Dr. Huda Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Howard Hughes Medical Institute investigator and Dr. Ralph D. Feigin professor at Baylor College of Medicine.

The award was presented jointly to Zoghbi and Dr. Adrian P. Bird, Buchanan professor of Genetics at the University of Edinburgh, during a special ceremony on September 27 in Hong Kong for their groundbreaking discovery of the genes and the encoded proteins associated with Rett syndrome.

Considered the “Nobel Prize of the East,” the Shaw Prize is an international award established in 2002 designed to foster scientific research. Awarded annually, the prize honors individuals who have achieved significant breakthroughs in academic and scientific research or applications and whose work has resulted in a positive and profound impact on mankind.

“I am humbled to be honored by the esteemed Shaw Prize Foundation,” Zoghbi said. “We will use this support to continue the research into how Rett syndrome affects the brain with the hope that our research will impact future treatment options.”

Rett syndrome is the leading cause of intellectual disabilities in girls, affecting one in 10,000, and is particularly devastating as girls affected by the syndrome develop normally for the first few months of life before a catastrophic decline in neurological capabilities.

Zoghbi’s discovery that mutations in the MEPC2 gene cause this devastating neurological disorder paved the way for the development of a diagnostic genetic test for Rett syndrome.

The $1.2 million Shaw prize will be shared by Bird and Zoghbi to advance Rett syndrome research.

August 1, 2016

8316chroniclephilanthropy250Texas Children’s is the honored sponsor for every Tuesday’s “Houston Legends” series. For more than 20 weeks, we will showcase the legendary care Texas Children’s has provided since 1954, and focus on milestone moments in our unique history. Also, a complementary website offers a more detailed look at our past, our story and our breakthroughs.

On the right is the Texas Children’s ad that is featured in this week’s Chronicle. Click the ad to visit our companion website at texaschildrens.org/legendarycare. The website will change weekly to complement the newspaper ad, which will be published in section A of the Chronicle on Tuesdays for the next 10 weeks. We also will spotlight this special feature weekly on Connect, so stay tuned to learn and share our rich history.

Click here to visit the Promise website.

June 14, 2016

102317Zoghbi175On May 31, The Shaw Prize Foundation in Hong Kong awarded the 2016 Shaw Prize in Life Science and Medicine to pioneering neuroscientist Dr. Huda Y. Zoghbi, director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Howard Hughes Medical Institute investigator, and Ralph D. Feigin Professor at Baylor College of Medicine.

The award was presented jointly to Zoghbi and Dr. Adrian P. Bird, Buchanan professor of Genetics at the University of Edinburgh, for their groundbreaking discovery of the genes and the encoded proteins associated with Rett syndrome.

“I am humbled to be honored by the esteemed Shaw Prize Foundation,” Zoghbi said. “We will use this support to continue the research into how Rett syndrome affects the brain with the hope that our research will impact future treatment options.”

Rett syndrome is the leading cause of intellectual disabilities in girls, affecting one in 10,000, and is particularly devastating as girls affected by the syndrome develop normally for the first few months of life before a catastrophic decline in neurological capabilities.

The Shaw Prize is an international award established in 2002 designed to foster scientific research. Awarded annually, the Prize honors individuals who have achieved significant breakthroughs in academic and scientific research or applications, and whose work has resulted in a positive and profound impact on mankind.

Zoghbi will receive the award, along with Bird, at a ceremony later this year in Hong Kong. The $1.2 million prize will be shared by Bird and Zoghbi.

Zoghbi’s discovery that mutations in the MEPC2 gene cause this devastating neurological disorder paved the way for the development of a diagnostic genetic test for Rett syndrome.