TAG: "Pediatrics"

UCLA researcher pioneers cure for ‘Bubble Baby’ disease


Game-changing stem cell treatment to be tested for sickle cell disease next.

Christian and Alysia Padilla-Vaccaro and their twins, Annabella (left) and Evangelina. With a newly restored immune system, Evangelina lives a normal and healthy life.

By Peter Bracke, UCLA

UCLA stem cell researchers have pioneered a stem cell gene therapy cure for children born with a life-threatening condition called adenosine deaminase–deficient severe combined immunodeficiency, or ADA-deficient SCID. Often called Bubble Baby disease, the condition can be fatal within the first year of life if left untreated.

The groundbreaking treatment was developed by Dr. Donald Kohn, a renowned stem cell researcher and member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

Kohn’s breakthrough was developed over three decades of research aimed at creating a gene therapy that safely restores the immune systems of children with ADA-deficient SCID using the patients’ own cells with no side effects.

To date, 18 children with SCID have been cured of the disease after receiving the therapy in clinical trials at UCLA and the National Institutes of Health.

“All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy,” said Kohn, a professor of pediatrics and of microbiology, immunology and molecular genetics in the UCLA College. “Instead they are all thriving with fully functioning immune systems.”

Children born with SCID are kept in controlled, isolated environments because without an immune system, ordinary illness and infection could be lethal.

“Other current options for treating ADA-deficient SCID are not always optimal or feasible for many children,” Kohn said. “We can now, for the first time, offer these children and their families a cure, and the chance to live a full, healthy life.”

Defeating ADA-deficient SCID

Children born with SCID, an inherited immunodeficiency, are generally diagnosed when they are about six months old. The disease causes their cells to not create ADA, an enzyme that is critical for producing the healthy white blood cells needed for a normal, fully functioning immune system. About 15 percent of all SCID patients are ADA-deficient.

Currently, there are only two treatment options for children with the disease. They can be injected twice a week with ADA — a lifelong process that is very expensive and often doesn’t return the immune system to optimal levels. Or they can undergo bone marrow transplants from siblings, but bone marrow matches are very rare and can result in the patient’s body rejecting the transplanted cells, which then turn against the child.

Since 2009 and over the course of two multiyear clinical trials, Kohn and his team tested two therapy regimens on 18 children with ADA-deficient SCID. The children’s blood stem cells were removed from their bone marrow and genetically modified to correct the defect.

All 18 patients were cured.

Using a virus delivery system that he developed in his lab in the 1990s, Kohn inserted the corrected gene that produces the missing enzyme into the blood, forming stem cells in the bone marrow. The genetically corrected blood-forming stem cells then produced T cells capable of fighting infection.

Kohn and his colleagues tested, modified and perfected viral delivery as the best method to put the healthy ADA genes back into the bone marrow cells of the patients. With the newly transplanted cells now able to produce the needed enzyme, the research team harnessed the powerful self-renewal potential of stem cells to repopulate the blood stream and the children developed their own new, fully functioning immune systems.

“We were very happy that over the course of several clinical trials and after making refinements and improvements to the treatment protocol, we are now able to provide a cure for babies with this devastating disease using the child’s own cells,” Kohn said.

The researchers’ next step is to seek FDA approval for the gene therapy, with the hope that all children with ADA-deficient SCID will be able to benefit from the treatment. Their cutting-edge research also lays the groundwork for the gene therapy to be tested for treatment of sickle cell disease; clinical trials are set to begin in 2015.

”We’ve been working for the last five years to take the success we’ve had with this stem cell gene therapy for SCID to sickle cell,” Kohn said. “We now have the potential to take the gene that blocks sickling and get it into enough of a patient’s stem cells to block the disease.”

UCLA Dr. Donald Kohn and Evangelina Padilla-Vaccaro

One child’s story

Only weeks after giving birth to fraternal twins in 2012, Alysia Padilla-Vaccaro quickly felt something was wrong with one of her daughters, Evangelina, now 2 years old.

“I was told that it was the stress, or the fear of being a new mom, but I just knew something wasn’t right,” said Padilla-Vaccaro, a resident of Corona, California. “Then I was informed that Evangelina had absolutely no immune system, that anything that could make her sick, would kill her. It was literally the worst time of my life.”

Alysia and her husband, Christian, brought Evangelina to UCLA. Soon after she underwent Kohn’s stem cell gene therapy, Evangelina’s new immune system developed without side effects. Her T cell count began to rise and her ability to fight off illness and infection grew stronger. Then Kohn told Alysia and Christian the good news: For the first time, they could hug and kiss their daughter and take Evangelina outside to meet the world.

“To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is,” Padilla-Vaccaro said. “I gave birth to my daughter, but Dr. Kohn gave my baby life.”

The research was supported by grants from the FDA, the California Institute for Regenerative Medicine and the National Institutes of Health, including the National Heart, Lung and Blood Institute; the National Institute of Allergy and Infectious Diseases; and the National Center for Advancing Translational Science.

Additional funding was provided by UCLA, including the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, the Jonsson Comprehensive Cancer Center, the Children’s Discovery and Innovation Institute, the department of microbiology, immunology and molecular genetics, and the department of pediatrics at the David Geffen School of Medicine.

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Building the future of health care


More than 1,000 donors give $131M in support of UC San Diego Jacobs Medical Center.

By Judy Piercey and Jade Griffin, UC San Diego

Committed to fostering the future of health care in San Diego, more than 1,000 donors have contributed $131 million to UC San Diego’s Jacobs Medical Center. Included in the total are gifts that matched a donation of $25 million, meeting the Challenge goal of the initiative.

Today (Nov. 20), the campus announced that the Challenge donation, originally anonymous, was made by Joan and Irwin Jacobs. They provided a $75 million lead gift for the new facility in 2010; with the Challenge gift, that brings their contributions to the Jacobs Medical Center to a total of $100 million. Continued private support will help fund the completion of the new medical center, which is the largest hospital project currently underway in Southern California.

Under construction and projected to open in 2016, Jacobs Medical Center is a $839 million, 10-story facility on the university’s La Jolla campus, which will include three new clinical care units in one location: The A. Vassiliadis Family Hospital for Advanced Surgery, The Pauline and Stanley Foster Hospital for Cancer Care and the Hospital for Women and Infants.

“We are deeply grateful to Joan and Irwin Jacobs for their generosity, including the recent $25 million match challenge,” said UC San Diego Chancellor Pradeep K. Khosla. “We also thank Carol Vassiliadis and Pauline Foster, who made leadership gifts, as well as all of the other donors who participated in meeting this challenge. These visionaries support UC San Diego’s commitment and vision to create a healthier world through new science, new medicine and new cures.”

“Jacobs Medical Center is part of a multibillion dollar university investment in the future of health care for the region,” said Dr. David A. Brenner, vice chancellor for Health Sciences and dean of the UC San Diego School of Medicine. “I want to thank all of the donors who have helped make this extraordinary medical center a reality.”

Irwin and Joan Jacobs

“When we came here in 1966, the medical school was just starting,” said Irwin Jacobs, co-founder, former chairman and CEO of Qualcomm Inc. and UC San Diego founding faculty member, who served as a professor in electrical and computer engineering from 1966 to 1972. “There was no hospital, just a school. So it’s very exciting to make Jacobs Medical Center possible. More and more, we’re learning how to bring results from basic research in biology and engineering to medicine, and to the clinic. I think this medical center is going to show how effective that can be. The innovations will spread out from San Diego, and go all around the world.”

The 509,500-square-foot facility will house 245 patient beds and be connected on multiple floors with the existing John M. and Sally B. Thornton Hospital on UC San Diego’s La Jolla campus, in the heart of the area’s nexus of biomedical research centers. Jacobs Medical Center has been designed with the patient in mind. From spacious private rooms to soothing color schemes and artwork, to next-generation medical equipment, the vision and needs of patients, doctors and nurses, all aspects of the Jacobs Medical Center have been fully integrated. Each floor will combine all the necessary healing elements while achieving optimal safety and efficient delivery of care.

“Soon we will have the largest, most technologically advanced hospital in the region, dedicated to offering specialized care for every kind of patient, in every phase of life,” said Paul Viviano, CEO of UC San Diego Health System.

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UCSF Mission Bay hospital complex to open Feb. 1


Three new hospitals for women, children and cancer patients.

UCSF Medical Center at Mission Bay will open Feb. 1, 2015. (Photo by Mark Citret)

After more than 10 years of planning and construction, UCSF Medical Center at Mission Bay will open Feb. 1, 2015 on UC San Francisco’s world-renowned biomedical research campus. UCSF Medical Center at Mission Bay comprises UCSF Benioff Children’s Hospital San Francisco, UCSF Betty Irene Moore Women’s Hospital and UCSF Bakar Cancer Hospital. The new facilities include a 289-bed hospital complex, with children’s emergency and outpatient services that will integrate research and medical advancements with patient-focused, compassionate care.​

UCSF Medical Center at Mission Bay will welcome its first patients the morning of Feb. 1, when teams of health care professionals and ambulances begin moving some inpatients from the UCSF Parnassus campus and Mount Zion campus into the new facilities.

The new medical center, strategically located on UCSF’s 60.2-acre Mission Bay research campus, will enhance UCSF’s ecosystem of innovation by putting physicians in close proximity to researchers and near biotechnology and pharmaceutical companies in Mission Bay and beyond. The new cancer hospital, for example, will sit near the UCSF Helen Diller Family Cancer Research Building, where every day leading scientists are seeking causes and cures for cancer.

UCSF Medical Center at Mission Bay also will feature the only operating hospital helipad in San Francisco to transport critically ill babies, children and pregnant women to the medical center from outlying hospitals.

“UCSF Medical Center at Mission Bay profoundly advances our ability to fulfill our mission as a public hospital, providing high-quality health care that meets the future needs of the entire Bay Area,” said Mark R. Laret, CEO, UCSF Medical Center and UCSF Benioff Children’s Hospitals. “By embedding clinical care within our research enterprise at Mission Bay, UCSF physicians and scientists in the forefront of cancer medicine, and women’s and children’s health will be able to more readily translate discoveries into next-generation therapies and cures.”

Each of the new hospitals’ designs reflects significant input from patients and families, as well as clinicians.

“UCSF Medical Center at Mission Bay sets a national benchmark for patient- and family-centered health care by offering an unparalleled healing environment that supports and connects patients and their families during hospital stays,” said Cindy Lima, executive director, UCSF Mission Bay Hospitals Project. “These new hospitals expand our capacity to provide the most advanced treatments in buildings that reflect input from the people who will use them.”

The hospitals feature state-of-the art technology, including the world’s largest hospital fleet of autonomous robotic couriers which will deliver linens, meals and medications. Interactive media walls in each private room will enable patients to communicate with their families and clinicians, and an imaging suite specially designed to eliminate anxiety during an MRI offers children the chance to virtually experience a San Francisco trolley ride, or to play with a cast of animated critters as they boat around the San Francisco Bay.

Distinctive features of UCSF Medical Center at Mission Bay include 4.3 acres of green space and 1.2 acres of rooftop gardens, soothing art- and light-filled interiors and a public plaza created in partnership with the City of San Francisco. In addition, UCSF Medical Center at Mission Bay is on target to be one of the first LEED Gold-certified hospital in California.

The Integrated Center for Design and Construction brought together more than 200 architects, engineers and contractors working side by side in a command center on the construction site. Construction of the hospitals began in December 2010.

“The healing power of UCSF Medical Center at Mission Bay extends beyond the hospitals’ walls, as clinicians and researchers work side by side to accelerate medical breakthroughs and transform the delivery of health care in this country,” said Sam Hawgood, M.B.B.S., chancellor of UC San Francisco. “It’s important to note that the hospital complex was built only through the generous philanthropic support of the Bay Area community, who share our vision of advancing health care across the world. We are greatly appreciative of their unwavering commitment to our mission over the past decade. ”

UCSF Benioff Children’s Hospital San Francisco

UCSF Benioff Children’s Hospital San Francisco, one of the nation’s leading children’s hospitals, provides treatment for virtually all pediatric conditions, as well as for critically ill newborns. The Neonatal Intensive Care Nursery at UCSF Benioff Children’s Hospital San Francisco was one of the first of its kind in the world. The hospital is the only California state-designated children’s medical center in San Francisco and is affiliated with UCSF Benioff Children’s Hospital Oakland.

The new 183-bed facility at Mission Bay creates an environment where children and their families find quality care at the forefront of scientific discovery. Private rooms in the intensive care nursery support the youngest patients, while the fully accredited classroom and teachers enable school-age patients to continue their education while focusing on their health. The hospital offers accommodations for families of pediatric patients and nearby lodging for those requiring longer stays.

UCSF Bakar Cancer Hospital

UCSF ranks consistently among the top cancer care centers in the nation, according to the “America’s Best Hospitals” survey from U.S. News & World Report. UCSF Bakar Cancer Hospital sets the standard in personalized care, delivering advanced cancer therapies tailored to individual patient needs. The hospital increases UCSF’s inpatient and outpatient capacity to meet growing demand, in a state-of-the-art facility. The new hospital will absorb many of the cancer surgery beds currently located at UCSF Medical Center at Mount Zion, offering cancer surgeries in specialties ranging from urology and orthopedics, to head and neck and gynecologic oncology. Specialists also serve the individual needs of cancer patients from the children’s and women’s hospitals. In the future, Mission Bay could house as many as 250 or more surgery beds, with a full complement of outpatient cancer care services.

UCSF Betty Irene Moore Women’s Hospital

As the region’s first dedicated women’s hospital, UCSF Betty Irene Moore Women’s Hospital will embody the philosophy of the UCSF National Center of Excellence in Women’s Health. The new hospital will deliver care that addresses health needs across a woman’s lifetime, including cancer treatment, specialty surgery, a 36-bed birth center, nine deluxe labor and delivery rooms, and select outpatient services. Customizing care to each patient, the hospital will provide the best available diagnostic tests and treatments in a caring, women- and family-focused environment that incorporates the latest technology. Spacious rooms allow loved ones to spend the day or night comfortably.

Each labor and delivery room is designed to be respectful to patients and families during the life-altering event of childbirth. Combining sophisticated technical capabilities with carefully considered design choices, each room emits a sense of calm for the birthing experience. At the same time, it is a highly functional space for clinicians to provide quality care.

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Are children better off than they were 25 years ago?


UCLA publishes comprehensive analysis of children’s rights around the world.

Jody Heymann, UCLA

Twenty-five years ago this month, the countries that compose the United Nations reached a landmark agreement that laid the foundation for much-needed strengthening of children’s rights and protections in nearly every country around the world.

Today, the Convention on the Rights of the Child remains the only formal global effort to improve children’s rights and the most widely ratified human rights treaty in history. Only three U.N. member nations have not ratified the treaty: Somalia, South Sudan and the United States.

“The Convention on the Rights of the Child is a promise from our global community to all children,” said Dr. Jody Heymann, founding director of the World Policy Analysis Center and dean of the UCLA Fielding School of Public Health. “Everyone deserves to know whether their country is fulfilling that promise and how it compares to other countries facing similar opportunities and constraints.”

To mark the 25th anniversary of the CRC on Nov. 20, the center assessed 190 U.N. countries’ progress toward fulfilling the CRC’s commitment to children in critical areas such as the right to education, protection from child labor and child marriage, and discrimination of children with disabilities.

How are the world’s children faring?

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New approach proposed to heart surgery for infants


Would potentially reduce the number of surgeries single-ventricle patients have to undergo.

A computer simulation showing how a clipped shunt would connect an artery off the aorta to the superior vena cava.

Engineers at the UC San Diego are proposing a new surgical intervention for children born with a single ventricle in their heart — instead of the usual two. The new approach would potentially reduce the number of surgeries the patients have to undergo in the first six months of life from two to just one. If successful, it would also create a more stable circuit for blood to flow from the heart to the lungs and the rest of the body within the first days and months of life.

Engineers ran computer simulations of the surgery and found it would reduce the workload on the patient’s heart by as much as half. It would also increase blood flow to the lungs and increase the amount of oxygen the body receives.

The surgery would introduce a radical change in the way infants with a single ventricle are treated. Currently, they undergo three surgeries by age three. Babies born with a single ventricle are severely deprived of oxygen, which makes their skin turn blue, and requires immediate medical intervention.

The research group, led by Alison Marsden, a professor of mechanical engineering, is working in collaboration with cardiothoracic surgeon Tain-Yen Hsia, of the Great Ormond Street Hospital for Children and UCL Institute of Cardiovascular Science in London.  They reported their findings in an October issue of the Journal of Thoracic and Cardiovascular Surgery.

“Even when surgeries are successful, these babies live with a circulation that is very taxing on the one heart pump they have,” Dr. Hsia said.  “So there is a need to find a better solution.”

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UCSF appoints first chief of the Division of Pediatric Emergency Medicine


David Jaffe also will serve as vice chair for pediatric emergency medicine.

David Jaffe

David M. Jaffe, M.D., has been appointed as the first chief of the Division of Pediatric Emergency Medicine (PEM) at UC San Francisco effective Feb. 1, 2015, the day the new  UCSF Benioff Children’s Hospital at Mission Bay opens. Jaffe also will serve as the department’s vice chair for pediatric emergency medicine.

“Dr. David Jaffe brings a rich history and wealth of expertise in pediatric emergency medicine that will take the UCSF program to new heights,” said Peter Sokolove, M.D., chair of the Department of Emergency Medicine.

The new UCSF Benioff Children’s Hospital at Mission Bay will offer specialized care for pediatric patients in a dedicated children’s emergency department. Equipped with the latest medical technology and a staff dedicated to the treatment and healing of children, it will provide pediatric patients with the care they need, when they need it.

Jaffe is currently the Dana Brown Professor of Pediatrics and director of the Division of Emergency Medicine at Washington University School of Medicine and St. Louis Children’s Hospital in St. Louis, Missouri. He was a founding member of both multi-institutional research networks in PEM, the Pediatric Emergency Medicine Collaborative Research Consortium (PEMCRC) and the federally funded Pediatric Emergency Care Applied Research Network (PECARN). His research interests include diagnosis and management of the febrile child, children with head and neck injuries, and management of procedure-associated pain and anxiety.

Jaffe has co-authored 69 original manuscripts and 115 abstracts. He is an associate editor of Annals of Emergency Medicine and a member of the Editorial Board of Pediatric Emergency Care. He is past chair of the Section on Emergency Medicine of the American Academy of Pediatrics (AAP) and past president of the Academic Pediatric Association.

Jaffe has held significant leadership roles on the American Board of Pediatrics, Pediatric Emergency Medicine Sub-board, Pediatric Residency Review Committee of the ACGME, and the planning committee of the annual PEM fellows conference. In 2006, he received the Jim Seidel Distinguished Service Award from the Section on Emergency Medicine of the AAP.

Jaffe received his bachelor’s degree from Stanford University and his M.D. from the University of Chicago Pritzker School of Medicine. He completed his pediatric residency training at the Children’s Hospital of Philadelphia, where he also trained as the first PEM fellow in the nation and as a Robert Wood Johnson fellow in Academic Pediatrics.

Prior to assuming his position at Washington University, Jaffe held academic positions at Northwestern University, Children’s Memorial Hospital, and was the PEM division head and ED director at the Hospital for Sick Children, University of Toronto. He will join UCSF after completing 24 years as the director of PEM at Washington University in St. Louis.

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Pediatric cancer expert champions innovative treatment at new hospital


UCSF researcher has helped redefine the treatment of neuroblastoma.

The entrance to the new UCSF Benioff Children's Hospital San Francisco at Mission Bay, which will open Feb. 1, 2015.

It offers whimsical works of art by celebrated artists, interactive exhibits designed by the Exploratorium and acres of rooftop gardens. When UCSF Benioff Children’s Hospital San Francisco moves to its new home at Mission Bay, it will even feature a fleet of robots that glide silently across hospital hallways bearing food trays or linens.

For most young patients, visits will be brief and occasional. But physicians like Kate Matthay, M.D., who runs the pediatric malignancies program, recognize that for some patients visits may be lengthy and frequent.

“The hospital is child friendly and family friendly, and that’s important because sick kids need their families close by,” said Matthay, who has been working at UCSF Benioff Children’s Hospital San Francisco since her fellowship in 1979 and is herself the parent of three adults.

Kate Matthay, UC San Francisco

Matthay is uniquely attuned to the needs of very sick children, because her patients include those with neuroblastoma, one of the most challenging pediatric cancers. Neuroblastoma is a rare malignancy of the nerve cells that usually starts in the adrenal glands, abdomen or near the spine by the chest or neck, spreading rapidly and aggressively in some patients. About 50 percent of patients present with advanced disease and require a bone-marrow transplant, follow-up therapy and lifelong specialized medical surveillance. Only 45 to 50 percent of patients over the age of 18 months with metastatic disease survive five years after diagnosis.

Matthay’s mission is twofold: She is committed to researching strategies that boost survival of neuroblastoma as well as other pediatric cancers with low cure rates; and she wants to identify the hallmarks of lower-risk disease that enable physicians to pare down treatment regimens, reducing side effects like hair loss, nausea and compromised immunity. More significantly, it will lower the risk of late effects, such as stunted growth, developmental delays and secondary cancers.

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UC Merced, community programs join to prevent obesity in families


Effort will focus on reducing obesity in young children.

In an effort to combat the increasing rates of obesity among Latino residents, UC Merced and the Merced County Central California Regional Obesity Prevention Program will join forces.

Funded by a three-year, $90,000 grant from National Institutes of Health’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, the campus and nonprofit will look at efforts in other areas that have scientifically proven successful in reducing obesity, particularly in young children.

They also will develop partnerships with community groups and hold public meetings to learn what obesity-related issues are of particular concern in the community. Forty-three percent of fifth-, seventh- and ninth-grade Merced County students were overweight or obese, according to the 2011 study A Patchwork of Progress.

“This is a powerful partnership that stands to benefit an underserved population within the San Joaquin Valley,” said psychology professor Jan Wallander, who co-authored the grant proposal. “By connecting talented researchers with community partners and members, we hope to help reduce the number of children who are plagued by this serious problem.”

The research project is an example of how the UC Merced Health Sciences Research Institute matches community needs with its multidisciplinary faculty affiliates. The research team will include Wallander, public health professor A. Susana Ramirez, sociology professor Zulema Valdez, anthropology professor Robin DeLugan and Blum Center interim Director Steve Roussos.

There are multiple challenges in helping people adopt healthy diets, said Claudia G. Corchado, program manager for the Central California Regional Obesity Prevention Program and lead community partner in the project. For example, some people believe chubby children are healthy children, she said, and others don’t fully understand the health impacts of high-sugar beverages.

“If we don’t understand what a calorie is, how can we understand and learn to control portion sizes?” Corchado said. “How can we know that a 20-ounce bottle of soda has 100 more calories than a can if we don’t know how to read and understand a nutritional label and what exactly that means to our overall health?”

In addition to education, Corchado said, some families need more access to fresh fruit and vegetables. Without nearby grocery stores, they must shop at corner stores that generally stock foods higher in fat, sodium and sugar, which cost less than healthier options.

“We’re living in a world of intervention, but we need to go back to a world of prevention,” she said. “We can teach Latino families to avoid obesity and diabetes through healthy eating and drinking habits.”

Corchado and Wallander hope the quarterly community forums are strongly attended. They’ll also organize an annual conference to share information and findings. With input from community groups and members, Wallander said, UC Merced researchers would likely have many projects they could pursue.

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New diagnostic test helps pinpoint mutations that cause rarest genetic diseases


Analysis scans all genes simultaneously to diagnose mystery conditions.

After doctors were unable to diagnose his mysterious condition, Calvin Lapidus (with his mom, Audrey) became the first person to undergo clinical exome sequencing at UCLA’s Clinical Genomics Center. (Photo by Lapidus family)

Audrey Lapidus adored her baby’s sunny smile and irresistible dimples. But when Calvin was 10 months old, suffering from chronic digestive problems and unable to roll over or crawl, she was worried.

Four neurologists were unable to determine the cause, and a battery of tests proved inconclusive. Desperate for answers, Audrey and her husband, Eric, brought Calvin to UCLA, where they agreed to have him become the first person at UCLA’s David Geffen School of Medicine to undergo a powerful new test called exome sequencing.

The test focuses on exomes, the protein-coding portions of genes that account for only 1 percent of DNA but nearly 85 percent of the glitches known to cause human diseases.

Using DNA collected from Calvin’s and his parents’ blood, a sophisticated sequencing machine rapidly scanned the boy’s genome, compared it to his parents’ and flagged a variant on his 18th chromosome. Calvin was diagnosed with Pitt-Hopkins Syndrome, a rare genetic disorder that affects only 250 children worldwide. At last, Audrey and Eric had a concrete diagnosis and clear direction for seeking the best treatment for their son.

Now a landmark UCLA study makes a persuasive argument for the routine clinical use of exome sequencing as a tool for diagnosing children with rare genetic disorders. Published online by the Journal of the American Medical Association, the findings show that exome sequencing produced a definitive diagnosis in 40 percent of UCLA’s most complex cases — a quantum leap from the field’s 5 percent success rate two decades ago.

“Our study is the first to show that sequencing a child’s genome together with his or her parents’ dramatically improves geneticists’ ability to reach a firm diagnosis in rare disorders,” said corresponding author Dr. Stan Nelson, vice chair of human genetics and a professor of pathology and laboratory medicine at David Geffen School of Medicine at UCLA. “We discovered a genetic cause for the conditions affecting 40 percent of the hundreds of young children who come to UCLA for exome sequencing due to developmental delays or intellectual disabilities.”

When it opened in 2011, the UCLA Clinical Genomics Center was one of just three facilities in the world putting DNA sequencing to clinical use. (The others are at the medical centers at Baylor University and Harvard University.)

Unlike earlier diagnostic tools that study one gene at a time, exome sequencing rapidly sifts through all of the 37 million base pairs in a person’s 20,000 genes to tease out the single DNA change that causes the genetic disorder.

For the two-year study, Nelson worked with first author Hane Lee, a UCLA assistant adjunct professor of pathology, to sequence and analyze the exomes of 814 children whose symptoms had baffled previous clinicians despite exhaustive genetic, biochemical and imaging tests. The researchers sequenced the genomes of each child and their parents and then funneled the raw data through high-powered computers and specialized software to identify variants from the standard human genome.

Next, the team filtered the data based on patients’ family histories and other relevant aspects of their conditions. The researchers pored through medical literature to find all genes and mutations linked to each patient’s symptoms. Finally, UCLA’s Genomics Data Board, a multidisciplinary team of experts, reviewed the findings to reach a diagnosis.

The entire process typically takes less than eight weeks, although tests have been completed within 10 days in medically urgent situations. With preauthorization, many insurance providers cover the cost to sequence a child and both parents. If not, the out-of-pocket fee is $6,650.

Audrey Lapidus said that having a diagnosis for Calvin “meant the world.” A former journalist, she investigated his disorder extensively, launched the Pitt-Hopkins Research Foundation and helped raise $1 million to fund research on the syndrome. She is passionate about promoting the availability of exome sequencing to parents and physicians, who often don’t inform families that the test is available.

Pitt-Hopkins Syndrome can cause delayed intellectual and motor skill development, breathing problems and seizures. Now an adorable 3-year-old, Calvin still cannot walk and may never speak. Still, Audrey Lapidus said she and Eric would rather know what to expect for their son than have to continue living in diagnostic limbo.

“All families deserve a clear diagnosis of their child’s condition,” said study co-author Dr. Wayne Grody, director of the UCLA Clinical Genomics Center and a professor of pathology, human genetics and pediatrics at the Geffen School of Medicine and Mattel Children’s Hospital UCLA. “Exome sequencing plays an important role in identifying the precise cause of a child’s illness. This is immediately useful to families and physicians in understanding how the disease occurred, preventing unnecessary testing, and developing the best strategies to treat it.”

The Clinical Genomics Center provides extensive counseling to guide families through the tests and prepare them for the results. The team also coordinates multidisciplinary care with UCLA specialists to address the medical complications associated with each child’s illness.

“Many parents of a child with a genetic disorder postpone getting pregnant for fear of passing the same disease on to future children,” said Naghmeh Dorrani, a UCLA genetic counselor and co-author of the study. “Exome sequencing can ease this concern by helping us to identify the risk of recurrence and offer parents appropriate prenatal testing options.”

The study’s other co-authors were Joshua Deignan, Samuel Strom, Sibel Kantarci, Fabiola Quintero-Rivera, Kingshuk Das, Traci Toy, Bret Harry, Michael Yourshaw, Michelle Fox, Brent Fogel, Julian Martinez-Agosto, Derek Wong, Vivian Chang, Perry Shieh, Christina Palmer, Katrina Dipple and Eric Vilain, all of UCLA. Several of the authors are affiliated with UCLA’s department of pathology and molecular medicine, which derives revenue from the clinical exome sequencing test.

The study was supported by grants from the National Center for Advancing Translational Science, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the California Institute of Regenerative Medicine and K12 Child Health Research Career Development Award, and the Hyundai Hope on Wheels Scholar Award.

For more information about clinical exome sequencing, contact the UCLA Clinical Genomics Center at (310) 267-2680.

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Researcher receives award from American Academy of Pediatrics


Randi Hagerman honored with one of most prestigious awards for pediatricians in U.S.

Randi Hagerman, UC Davis

Randi Jenssen Hagerman, medical director of the UC Davis MIND Institute, Distinguished Professor of Pediatrics and Endowed Chair in Fragile X Research and Treatment, has received the prestigious C. Anderson Aldrich Award in Child Development for her outstanding contributions in the field of child development from the American Academy of Pediatrics (AAP), the professional organization for pediatricians in the United States.

The award recognizes pediatricians and non-pediatricians for their respective contributions to the field of developmental and behavioral pediatrics. It was presented at the American Academy of Pediatrics Section on Developmental and Behavioral Pediatrics national conference in San Diego on Oct. 12.

I am greatly honored by this award, humbled  after reading the list of previous recipients, and pleased that the AAP recognizes the importance of targeted treatments for individuals with neurodevelopmental disorders,” Hagerman said.

Hagerman is an internationally recognized clinician/scientist, director of the clinical trials program and founder of the Fragile X Research and Treatment Center at the MIND Institute. In 2001, with her husband, Paul J. Hagerman, UC Davis Distinguished Professor of Biochemistry and Molecular Medicine, she discovered fragile X-associated tremor/ataxia syndrome (FXTAS), a neurological disorder that affects older carriers of the fragile X premutation. In 1984 she co-founded the National Fragile X Foundation.

“This award is well-deserved recognition for Dr. Hagerman’s lifelong commitment to children with fragile X syndrome and their families,” said Leonard Abbeduto, Tsakopoulos-Vismara Endowed Chair of psychiatry and behavioral sciences and director of the MIND Institute. “She has helped thousands of people directly through her clinical care, and countless more through her groundbreaking research on the causes, consequences and treatment of FMR1-related disorders.”

“She also has trained and mentored a generation of pediatricians who will carry the field forward for decades to come,” Abbeduto continued. “It is certainly fitting that Dr. Hagerman is added to the list of luminaries who have received this award before her.“

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UC Davis names chief of pediatric general, thoracic and fetal surgery


Shinjiro Hirose joins from UCSF.

Shinjiro Hirose

Shinjiro Hirose, a nationally recognized fetal and pediatric surgeon, has joined the faculty of the UC Davis School of Medicine as chief of the newly established Division of Pediatric General, Thoracic and Fetal Surgery in the Department of Surgery.

Before joining UC Davis, Hirose was the lead pediatric surgeon at the UC San Francisco Benioff Children’s Hospital and its Fetal Treatment Center, specializing in minimally invasive surgery for gastrointestinal, biliary, liver and thoracic disorders in fetuses in utero and children. He and his mentor, internationally renowned pediatric surgeon Diana Farmer, were key in developing the Fetal Treatment Center.

“With Shin’s arrival at UC Davis, we can now forge ahead in creating the first comprehensive fetal diagnosis and therapy center in the Sacramento region. Our ‘dream team’ is complete,” said Farmer, who is chair of the Department of Surgery and surgeon-in-chief at UC Davis Children’s Hospital.

“We are establishing a world-class center to serve the needs of the children in the Sacramento region, the Central Valley and beyond,” Hirose said. “I will be partnering with our existing pediatric surgery group to expand our specialty surgical services. I met with so many families from this area when I worked at UC San Francisco. Now, those families can receive the same level of expertise and care that they received in the Bay Area, but much closer to home.”

Hirose is one of the creators of the University of California Fetal Therapy Consortium, a statewide collaboration at all five of the fetal treatment programs at the University of California campuses with medical centers at Davis, San Francisco, Los Angeles, Irvine and San Diego.

In addition to his background in fetal medicine, he is a nationally recognized children’s cancer surgeon and an expert in the development and use of surgical robotics in children.

Hirose also has a joint appointment as director of pediatric surgery at Shriners Hospitals for Children – Northern California, where he will develop a surgical program to serve children with complex colorectal and pelvic floor anomalies and a bowel-management program.

Hirose earned his bachelor’s of science degree in mechanical engineering at the Massachusetts Institute of Technology and his medical doctorate from New York Medical College. He completed surgical residencies at UC Davis and UC San Francisco, a fellowship in fetal diagnosis and therapy at UC San Francisco, and a  fellowship in pediatric surgery at Columbia University in New York.

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Teens help family of girl with liver cancer


Westside teens ‘aiming to do good wherever good can be done’ aid UCLA patient, her family.

David Mezquita kisses his 4-year-old daughter Vicky, who has liver cancer and is undergoing treatment at Reagan UCLA Medical Center. To help the family pay for nursing care, an organization of Westside teenagers raised money through a garage sale.

When Myra and David Mezquita of the South Bay had triplets, they knew they were blessed even though they had their hands more than full caring for the new arrivals as well as their teenagers.

Then one of the triplets, Vicky, was diagnosed with liver cancer and needed a transplant, which was performed at UCLA in April 2013 by Dr. Ronald Busuttil, distinguished professor and executive chairman of the UCLA Department of Surgery. Things seemed to be going well at first. But sadly, less than a year later, Vicky was diagnosed with recurrent cancer in her new liver.

To eradicate some liver tumors that remained unaffected by the chemotherapy, the 4-year-old underwent chemotherapy and stereotactic body radiation therapy (SBRT), a newer radiation treatment that noninvasively focuses high doses of radiation to kill tumors in a few treatment sessions.

The Mezquitas were juggling treatment appointments and caring for their other children when they lost crucial supplemental funding they had used to pay for nursing care for Vicky. Piling onto the family’s troubles, a utility-sparked fire that occurred about the time of Vicky’s transplant destroyed their backyard, including all the fencing and landscaping, leaving the children no safe place to play. Because of Vicky’s need for intense care following the transplant, no repairs were ever made, said her mother Myra Mezquita.

Members of Teamwork Makes the Dream Work join medical staff and family members at Vicky Mezquita's bedside in Reagan UCLA Medical Center.

Fortunately, some Westside teens who raise money to help sick children through a charity they co-founded, Teamwork Makes the Dream Work, found out about the family’s plight. Guided by the organization’s motto, “Aiming to do good wherever good can be done,” they held their annual garage sale and raised more than $5,100 for Vicky’s family, money that will help them augment her nursing care and create a new backyard for Vicky and her siblings to enjoy.

“We went all over the Westside, from Santa Monica to West Hollywood, gathering donations for the garage sale,” group member Nahal Shakib, 19, of Pacific Palisades said. “It was really important to us to raise a lot of money.”

Shakib and three members from Brentwood — Jasmine Shaouli, 18; Leila Aframian, 17; and Devon Shalom, 17 —  recently presented a check to David Mezquita, who was visiting his daughter while she was in Reagan UCLA Medical Center because of a low white blood cell count caused by the chemotherapy. The teens also brought gifts for Vicky’s siblings as well.

Dr. Julie Kang, a resident in the Department of Radiation Oncology, was able to connect the teens with the Mezquita family through a mutual friend. Kang was there when the check and gifts were presented to the family, along with Vicky’s radiation oncologist, Dr. Percy Lee, who oversaw the radiation treatments, and nurse Adriana Grandpre-Aguiar, who assisted with her care.

“It takes a lot of help to make good things happen,” the grateful father said. “I’m very happy and pleased that everyone joined together as a team to make this happen. I’m very touched.”

Myra Mezquita said that, at times, the circumstances her family is dealing with are “beyond imaginable. I can’t express the magnitude of our gratitude for the support we received from everyone.”

Lee, an associate professor of radiation oncology and director of UCLA’s SBRT program, said he was pleased they were able to treat all the visible cancer with the new radiation therapy. “This little girl has been through a lot in the last four years, and we are hopeful that the treatments give her a fighting chance,” he said.

Lee added that he was glad the family was getting some financial assistance. Even with their money woes, he said, the Mezquita family had recently given him a thoughtful gift card to pay for his lunch at a local eatery.

Kang said it was difficult watching the Mezquitas guide their child through a second bout of liver cancer.

“Parents can sometimes feel so alone in this big battle,” she said. “It’s beyond amazing that these angels came out of nowhere to help them out.”

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