Press Releases

Ten Children’s Hospitals Unite to Change Pediatric Care Through Genomic Medicine

Rady Children’s among founding members of innovative consortium

SIOUX FALLS, S.D. — Nov. 5, 2019— Three more hospitals have signed on to rapidly integrate genetics and genomics into primary and specialty pediatric care through an innovative consortium with Sanford Health.

Rady Children’s Hospital and Rady Children’s Institute for Genomic Medicine are founding members of the Sanford Children’s Genomic Medicine Consortium.

The new hospitals are Lucile Packard Children’s Hospital Stanford, Palo Alto, California; Seattle Children’s Hospital; and American Family Children’s Hospital, UW Health, in Madison, Wisconsin. That brings the total number in the consortium to 10.

The mission of the consortium is to efficiently manage resources in genetics and genomics, perform cutting-edge research and education and bring genomic medicine into pediatric practice. This will help set the standard for precision medicine in children’s health care.

In addition to Rady Children’s, the other member hospitals include Sanford Children’s (Sioux Falls and Fargo), Children’s Minnesota (Minneapolis and St. Paul), Children’s Hospital Colorado (Aurora), Children’s Hospital Los Angeles, Banner Children’s at Diamond Children’s Medical Center (Tucson) and Nicklaus Children’s Hospital (Miami).

Previous innovation projects funded by the consortium include a study of the outcomes of rapid whole genomic sequencing in critically ill newborn infants and a study evaluating the routine use of an extensive, pediatric-focused, next generation sequencing panel in the diagnosis of childhood cancers.

Genetic diseases are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU, PICU). These children often undergo an extensive and expensive diagnostic process that may not lead to a final diagnosis.

Stephen Kingsmore, M.D., D.Sc., president and CEO of Rady Children’s Institute of Genomic Medicine (RCIGM), is leading rapid whole genomic sequencing in critically ill newborn infants to determine the complete DNA sequence of a child’s genome at one time to identify the risk of genetic diseases.

Currently, the average turnaround time for sequencing to diagnosis by the RCIGM team is under a week. That is significantly faster than the common timetable for this type of work, which can take weeks to complete. “The future of pediatric medicine is being transformed by the ability to rapidly decode the genomes of the most fragile newborns to deliver exact diagnoses and targeted treatment,” Dr. Kingsmore said.

Pediatric cancers have different genetic origins compared with adult cancers. Current panels for detecting the genetic origins of a tumor primarily focus on adult cancers. OncoKids® developed at Children’s Hospital Los Angeles, is specifically formulated to detect the genomic alterations of pediatric cancers including leukemias, lymphomas, bone, soft tissue and brain tumors. “The ability to identify the precise underlying genomic alterations in individual tumors with OncoKids® allows us to personalize care and innovate how we treat children with cancer,” said Alexander R. Judkins, M.D., Pathologist-in-Chief and Executive Director of the Center for Personalized Medicine (CPM) at Children’s Hospital Los Angeles.

Extending precision medicine to children’s health through this consortium is inspired by the vision of Denny Sanford.

“We are thrilled to welcome these three additional premier children’s hospitals to the Sanford Children’s Genomic Medicine Consortium. I am thankful to each member for their strong support of the spirit of working together to more precisely care for each child using the cutting edge tools of genetics and genomics,” said Gene Hoyme, M.D., Medical Director, Sanford Children’s Genomic Medicine Consortium. “So much can be gained for the care of all children through the collaboration of these hospitals.”

About Sanford Health
Sanford Health, one of the largest health systems in the United States, is dedicated to the integrated delivery of health care, genomic medicine, senior care and services, global clinics, research and affordable insurance. Headquartered in Sioux Falls, South Dakota, the organization includes 44 hospitals, 1,400 physicians and more than 200 Good Samaritan Society senior care locations in 26 states and nine countries. Nearly $1 billion in gifts from philanthropist Denny Sanford have transformed how Sanford Health improves the human condition. For information, visit sanfordhealth.org or Sanford Health News.

Contact:
Jacqueline Palfy, Sioux Falls
Sanford Health Media Relations
605-366-2432 / jacqueline.palfy@sanfordhealth.org

Rady Children’s Institute for Genomic Medicine Receives $3 Million Grant to Investigate the Role Genes Play in Heart Muscle Disease

Four-year National Institutes of Health Grant to Focus on Cardiomyopathy Research

 SAN DIEGO – Sept. 27, 2019 – The National Institutes of Health has awarded Rady Children’s Institute for Genomic Medicine (RCIGM) a four year, $3,049,054 grant to investigate how genetic interactions may influence cardiomyopathy (CM), a devastating heart disease that affects millions in the United States, with about 200,000 new cases diagnosed annually.

“Our research seeks to better understand how multiple genes work together to increase the severity and risk of getting cardiomyopathy, which will impact more than one in every 500 people during their lifetimes,” said Matthew Bainbridge, principal investigator and associate director of clinical genomics at RCIGM. “Gaining a better understanding of the genetic mechanisms that influence cardiomyopathy will help medical professionals give better treatments and advice to patients.”

Currently, genetic diagnoses of CM often fail to predict severity or incidence of heart failure, significantly increasing the likelihood of death in CM patients. This is driven, in part, by poor understanding of genetic interactions in CM.  RCIGM researchers will test the hypothesis that multiple genetic mutations can lead to a more severe presentation of CM and investigate whether variants that are seemingly benign may actually cause more severe disease in combination with known mutations, with the ultimate goal of improving the ability to predict how the disease will manifest in CM patients based on their unique genetic information.

The research will also provide critically needed data to help generate computational models to predict inheritance of traits that are influenced by more than one gene (polygenic) and build infrastructure to conduct large scale tests for polygenic inheritance in CM.

Research will involve using data from existing cohorts of CM patients, both from Rady Children’s Hospital-San Diego and public databases.  Additionally, RCIGM will whole genome sequence 40 Rady Children’s CM patients in order to identify the best candidates to be tested against combinations of seemingly benign gene variants and those known to cause disease.  Finally, the three best candidates will be assessed in a mouse model.

“Unlike other conditions with clear causes, cardiomyopathy is complicated, with over-lapping genetic causes that can result in a widely different course of disease,” said Bainbridge. “While some CM patients can effectively manage their condition with medications, others may develop heart failure necessitating heart transplant.  With a better understanding of how genes work together, we can more effectively determine a patient’s prognosis.”

The NIH grant will distributed over a four year period with an average annual payment of approximately $762,000.

“The leading edge research underway at Rady Children’s Institute for Genomic Medicine is focused on revealing the causes for genetic disease, and offering insight into disease-specific interventions to help guide care,” said Stephen Kingsmore, MD, DSc, President and CEO of RCIGM. “This innovative approach to understanding the role genes play in cardiomyopathy could lead to better treatments and better quality of life for patients. And that’s what RCIGM is all about.”

Research reported in this news release was supported by the National Heart, Lung And Blood Institute of the National Institutes of Health under Award Number R01HL145175. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

New Research Award Supports Early Career Investigator of Childhood Digestive Diseases

Funded 3-year appointment at Rady Children’s Institute for Genomic Medicine

June 17, 2019—San Diego – A new research scholar position at Rady Children’s Institute of Genomics Medicine (RCIGM) has been awarded to a talented young investigator who is pursuing a career using genomics to enhance understanding of pediatric digestive diseases.

Amy Hemperly, DO, is the first recipient of the Research Scholar Award in Pediatric Genomics offered jointly by RCIGM and the American Gastroenterological Association (AGA). A graduate of UC San Diego, Hemperly will serve as principal investigator for the three-year project starting in July.

“My career goal is to become an independent physician scientist,” she said. “This award will give me protected time and resources to study the influence of genetic variations on response to drug treatment in patients with pediatric IBD.”

Over the course of her project, she will also work closely with the Institute’s senior investigators and be mentored in clinical and translational pediatric genomics.

“We are delighted that Dr. Hemperly will be joining RCIGM to pursue her career as a physician-scientist. She is a very talented and intelligent individual who will be a true asset to our team as we strive to improve the health of generations to come,” said Charlotte Hobbs, MD, Vice President of Research and Clinical Management.

AGA scholar awards have launched the careers of young investigators doing important work that translates to new patient care tools for clinicians and better outcomes for patients.

“The 2019 class of AGA Research Foundation awardees represents some of the most innovative and promising early-stage investigators working in the field of gastroenterology,” said Robert S. Sandler, MD, MPH, AGAF, chair, AGA Research Foundation. “We’re proud to support these individuals as they continue on their ultimate mission to improve the treatment and care of digestive disease patients through their discoveries.”

The awards program is made possible thanks to generous donors and funders contributing to the AGA Research Foundation. Learn more about the AGA Research Foundation at www.gastro.org/foundation.

About Rady Children’s Institute for Genomic Medicine

The Institute is leading the way in advancing precision healthcare for infants and children through genomic and systems medicine research. Discoveries at the Institute are enabling rapid diagnosis and targeted treatment of critically ill newborns and pediatric patients at Rady Children’s Hospital-San Diego and partner hospitals. The vision is to expand delivery of this life-saving technology to enable the practice of precision pediatric medicine at children’s hospitals across California, the nation and the world. RCIGM is a subsidiary of Rady Children’s Hospital and Health Center. Learn more at www.RadyGenomics.org. Follow us on Twitter and LinkedIn.

About the AGA Institute

The American Gastroenterological Association is the trusted voice of the GI community. Founded in 1897, the AGA has grown to more than 16,000 members from around the globe who are involved in all aspects of the science, practice and advancement of gastroenterology. The AGA Institute administers the practice, research and educational programs of the organization. www.gastro.org.

About the AGA Research Foundation

The AGA Research Foundation, formerly known as the Foundation for Digestive Health and Nutrition, is the cornerstone of AGA’s effort to expand digestive disease research funding. Since 1984, the AGA, through its foundations, has provided more than $51 million in research grants to more than 950 scientists. The AGA Research Foundation serves as a bridge to the future of research in gastroenterology and hepatology by providing critical funding to advance the careers of young researchers between the end of training and the establishment of credentials that earn National Institutes of Health grants. Learn more about the AGA Research Foundation or make a contribution at www.gastro.org/foundation.

Rady Children’s Institute for Genomic Medicine Uses Artificial Intelligence to Diagnose Genetic Diseases

April 24, 2019–Researchers at Rady Children’s Institute for Genomic Medicine (RCIGM) have utilized automated machine-learning and clinical natural language processing (CNLP) to diagnose rare genetic diseases in record time. This new method is speeding answers to physicians caring for infants in intensive care and opening the door to increased use of genome sequencing as a first-line diagnostic test for babies with cryptic conditions.

“Some people call this artificial intelligence, we call it augmented intelligence,” said Stephen Kingsmore, MD, DSc, President and CEO of RCIGM. “Patient care will always begin and end with the doctor. By harnessing the power of technology, we can quickly and accurately determine the root cause of genetic diseases. We rapidly provide this critical information to intensive care physicians so they can focus on personalizing care for babies who are struggling to survive.”

A new study documenting the process was published today in the journal Science Translational Medicine. The workflow and research were led by the RCIGM team in collaboration with leading technology and data-science developers —Alexion, Clinithink, Diploid, Fabric Genomics and Illumina.

Dr. Kingsmore’s team has pioneered a rapid Whole Genome Sequencing process to deliver genetic test results to neonatal and pediatric intensive care (NICU/PICU) physicians to guide medical intervention. RCIGM is the research arm of Rady Children’s Hospital-San Diego.

By reducing the need for labor-intensive manual analysis of genomic data, the supervised automated pipeline provided significant time-savings. In February 2018, the same team achieved the Guinness World Record™ for fastest diagnosis through whole genome sequencing. Of the automated runs, the fastest times – averaging 19 hours – were achieved using augmented intelligence.

“This is truly pioneering work by the RCIGM team—saving the lives of very sick newborn babies by using AI to rapidly and accurately analyze their whole genome sequence “ says Eric Topol, MD, Professor of Molecular Medicine at Scripps Research and author of the new book Deep Medicine.

RCIGM has optimized and integrated several time-saving technologies into a rapid Whole Genome Sequencing (rWGS) process to screen a child’s entire genetic makeup for thousands of genetic anomalies from a blood sample.

Key components in the rWGS pipeline come from Illumina, the global leader in DNA sequencing, including Nextera DNA Flex library preparation, whole genome sequencing via the NovaSeq 6000 and the S1 flow cell format. Speed and accuracy are enhanced by Illumina’s DRAGEN (Dynamic Read Analysis for GENomics) Bio-IT Platform.

Other pipeline elements include Clinithink’s clinical natural language processing platform CliX ENRICH that quickly combs through a patient’s electronic medical record to automatically extract comprehensive patient phenotype information.

Another core element of the machine learning system is MOON by Diploid. The platform automates genome interpretation using AI to automatically filter and rank likely pathogenic variants. Deep phenotype integration, based on natural language processing of the medical literature, is one of the key features driving this automated interpretation. MOON takes five minutes to suggest the causal mutation out of the 4.5 million variants in a whole genome.

In addition, Alexion’s rare disease and data science expertise enabled the translation of clinical information into a computable format for guided variant interpretation.

As part of this study, the genetic sequencing data was fed into automated computational platforms under the supervision of researchers. For comparison and verification, clinical medical geneticists on the team used Fabric Genomics’ AI-based clinical decision support software, OPAL (now called Fabric Enterprise)—to confirm the output of the automated pipeline. Fabric software is part of RCIGM’s standard analysis and interpretation workflow.
The study titled “Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation,” found that automated, retrospective diagnoses concurred with expert manual interpretation (97 percent recall, 99 percent precision in 95 children with 97 genetic diseases).

Researchers concluded that genome sequencing with automated phenotyping and interpretation—in a median 20:10 hours—may spur use in intensive care units, thereby enabling timely and precise medical care.
“Using machine-learning platforms doesn’t replace human experts. Instead it augments their capabilities,” said Michelle Clark, PhD, statistical scientist at RCIGM and the first author of the study. “By informing timely targeted treatments, rapid genome sequencing can improve the outcomes of seriously ill children with genetic diseases.”

An estimated four percent of newborns in North America are affected by genetic diseases, which are the leading cause of death in infants. Rare genetic diseases also account for approximately 15 percent of admissions to children’s hospitals.

The RCIGM workflow is engineered to speed and scale up genomic data interpretation to reduce the time and cost of whole genome sequencing. The team’s goal is to make rWGS accessible and available to any child who needs it.

Increased automation of the process removes a barrier to scaling up clinical use of WGS by reducing the need for time-consuming manual analysis and interpretation of the data by scarce certified clinical medical geneticists. There were fewer than 1,600 of these experts nationwide in 2017, according to the American Board of Medical Genetics and Genomics.

Rady Children’s Institute began performing genomic sequencing in July 2016. As of the end of March 2019, the team had completed testing and interpretation of the genomes of more than 750 children. One-third of those children have received a genetic diagnosis with 25 percent of those benefitting from an immediate change in clinical care based on their diagnosis.

Rady Children’s Institute for Genomic Medicine Appoints Six New Members to Board of Directors

The Rady Children’s Institute for Genomic Medicine (RCIGM) is pleased to announce the appointment of six new members to the Institute’s Board of Directors.

“Each of these dynamic innovators brings extensive experience in providing strategic leadership and oversight to highly successful organizations,” said Dr. Stephen Kingsmore, president and CEO of the Institute. “Their guidance will help us prepare for future success as the Institute continues to grow and develop.”

David F. Hale, chairman of the Institute’s Board of Directors, likewise applauded the addition of the new trustees. “It’s our good fortune to welcome these accomplished individuals to the Board of the Institute,” he said. “Their commitment to excellence will help propel us toward our goal of transforming pediatric medicine.”

RCIGM is the research arm of Rady Children’s Hospital-San Diego. The Institute was founded with the mission of enabling the diagnosis, treatment and targeted clinical care for newborns and children with rare, life-threatening diseases. The Institute is focused on delivering molecular diagnoses through rapid Whole Genome Sequencing (rWGS) to facilitate fast, precise medical care of the most fragile young patients.

The Institute has continued to expand their impact on the world of advanced pediatric genomic medicine, and there is growing recognition for the groundbreaking work, from speed records, to legislative proclamations, to grant awards and scientific distinctions. The Institute is also dedicated to shaping the future of rapid precision medicine by providing educational expertise through ongoing training and mentoring opportunities, annual conferences and educational series.

The Board of Directors has been established to provide strategic oversight and guidance to the Institute. Each new member of the Board will serve a three-year term and bring the board roster to 18 members. The six newly appointed members are as follows:

1. Joe Beery
Senior Vice President and Chief Information Officer
Thermo Fisher Scientific
He is an instrumental leader who cultivates unified culture, and has focused on improving operational reliability and innovative strategies. He was named Senior Vice President of Information Technology and Chief Information Officer following his role as leader of global Information Technology infrastructure. He has spearheaded the merger of multiple organizations through the development and operation of I.T. systems and e-commerce platforms. He holds a B.A. in Business Administration and Business Computer Systems from the University of New Mexico.

2. Scott D. Kahn, PhD
Chief Information Officer
Luna PBC
He is an expert in informatics and data science strategy. Prior to his current role, he was Illumina’s first Chief Information Officer, and was an executive leader in Illumina’s Enterprise Informatics Unit. He holds a PhD in Theoretical Organic Chemistry from UC Irvine and was a Fellow Commoner of Churchill College at the University of Cambridge in England.

3. Donald B. Kearns, MD, MMM
President Emeritus
Rady Children’s Hospital and Health Center
He is a pediatric otolaryngologist who recently retired as CEO of Rady Children’s Hospital and Health Center. He had previously served Rady in various leadership positions including Chairman of the Department of Surgery, Surgeon-in-Chief and Chief Medical Officer. Dr. Kearns earned his medical degree from Louisiana State University School of Medicine and was awarded a Master of Medical Management degree from the Marshall School of Business at the University of Southern California.

4. Frederic B. Luddy
Founder and Chairman of the Board of Directors
ServiceNow
He is an innovative entrepreneur with expertise in the growth and development of organizations. He founded ServiceNow in 2004, an enterprise software company that was ranked No. 1 on the 2018 Forbes Most Innovative Companies list. He stepped down as CEO in 2011 to focus on product development and now serves in an advisory capacity.

5. Trindl Reeves, CIC, AAI
Principal
Marsh & McLennan Insurance Agency
She has over 30 years of experience providing leadership and expertise in risk management and health and welfare consulting, and has held numerous leadership positions. She is responsible for leading the firm’s company wide sales effort and has played a key role in the company’s rapid growth. In 2011, she was named one of San Diego Business Journal’s Women Who Mean Business. She earned a B.A. in psychology from the University of California, Irvine, and holds the professional designations of Certified Insurance Counselor (CIC) and Accredited Advisor in Insurance (AAI).

6. Jon Soderstrom, PhD
Managing Director, Office of Cooperative Research
Yale University
He is responsible for defining and executing commercialization strategies including negotiation of licenses and corporate-sponsored research agreements, initiating strategic corporate partnerships, and development and marketing of new spin-off companies to the venture investment community. Since joining the Office in 1996, he has helped form 30 new ventures. Dr. Soderstrom was honored as the 87th “Point of Light” by President George H. W. Bush in March, 1990 for volunteer work with low-income families in East Tennessee to build and rehabilitate housing and provide other essential services. He received his Ph.D. from Northwestern University in 1980 and his B.A. from Hope College in 1976.

RCIGM Scientists Detect Cause of Rare Pediatric Brain Disorder

Rady Children’s Institute for Genomic Medicine Leads Mutation Discovery

Feb. 20, 2019—An international effort led by physician-scientists at Rady Children’s Institute for Genomic Medicine (RCIGM) has identified the cause of a devastating pediatric brain disorder paving the way for the first step in developing potential therapies for this rare neurodegenerative condition.

Investigators performed advanced genetic tests on blood samples from seven children with neuro-development disabilities who were evaluated by doctors in San Diego, Montreal and Cairo. This led to the discovery of mutations in the VARS gene, which had not previously been linked to human disease.

“These children showed epileptic seizures and abnormalities evident on brain MRI scans,” said Joseph Gleeson, MD, director of neurodevelopmental genetics at RCIGM and professor of neuroscience and pediatrics at UC San Diego School of Medicine. “Although no treatment currently exists for this condition, the results are important as the first step in guiding research directed at targeted therapies.”   

The genetic mutations identified in the study led to a defect in the enzyme responsible for generating proteins containing the amino acid valine which is necessary for cellular health. Genetic variations that damage these types of enzymes are associated with a variety of human diseases including microcephaly and neuropathy.

In this study, the team found that, enzymatic activity was significantly reduced in cells from the young patients. The findings suggest that children with this disorder may benefit from treatments to support the synthesis of new valine containing proteins in the brain.

For many children with genetic disabilities, the cause of their disease is never identified. This limits the ability of doctors to develop precise treatment plans. Researchers at RCIGM have pioneered the use of Whole Genome Sequencing to rapidly diagnose and guide medical management of rare childhood diseases.

Both whole exome and whole genome testing were conducted as part of this study. These tests search an individual’s genetic code for imperfections that are the source of disease.

“Trying new approaches to understand what these children have is important because it helps families when they have an answer about what it is that’s making their child so sick,” adds study co-author Geneviève Bernard, MD, MSc, FRCPc, pediatric neurologist at the Montreal Children’s Hospital of the McGill University Health Centre (MUHC) and a researcher with the Child Health and Human Development Program of the Research Institute of the MUHC.

Patient evaluation and testing for this study was conducted at Rady Children’s Hospital-San Diego, Montreal Children’s Hospital of the McGill University Health Centre and the National Research Center in Cairo. Medical research institutions in Amsterdam, Hong Kong, Qatar and Egypt also played a supporting role in confirming the biologic impact of the mutation in the VARS gene.

“For ultra-rare conditions such as this one, collaboration among multiple research institutions is crucial to confirm that changes identified in the genetic code may be common to multiple children with similar clinical symptoms,” said study co-author Jennifer Friedman, MD, neurologist at Rady Children’s Hospital and professor at UC San Diego School of Medicine.

“Such cooperation and patient matching plays a critical role in the identification of new genes and provision of diagnoses to geographically dispersed individuals with the same rare disorder,” Dr. Friedman said.

In future experiments, the researchers hope to test whether dietary supplementation with valine or gene therapy may help to restore the altered protein in the brain of these children.

Results of the study were published in the journal Nature Communications under the title “Biallelic mutations in valyl-tRNA synthetase gene VARS, are associated with a progressive neurodevelopmental epileptic encephalopathy.”  DOI: 10.1038/s41467-018-07067-3 https://www.nature.com/articles/s41467-018-07067-3

Rady Children’s Institute for Genomic Medicine Appoints New VP of Research

Dr. Charlotte A. Hobbs joins the executive leadership team

February 11, 2019—The Rady Children’s Institute for Genomic Medicine (RCIGM) is pleased to announce that physician-scientist Charlotte A. Hobbs, MD, PhD, has assumed the role of Vice President of Research and Clinical Management.

Dr. Hobbs brings a wealth of experience as a distinguished clinician, researcher, medical educator and hospital administrator. She has directed national studies of birth defects and pediatric health funded by NIH and CDC, among others. She recently completed a $6.1 million NIH-funded Genome Wide Association study involving more than 8,000 individuals in eight states.

“We are very pleased to have recruited Dr. Hobbs to join the Institute’s executive leadership,” said Stephen Kingsmore, MD, DSc, President and CEO of the Rady Children’s Institute for Genomic Medicine. “She brings deep expertise in building biomedical research programs and a passion for improving patient outcomes. That combination makes her uniquely qualified to join us in our mission to transform pediatric care.”

In her new role, Dr. Hobbs will guide the growing research and clinical programs at RCIGM. She will oversee the clinical genomics team, including physicians, nurses, genetic counselors and project managers, providing them with the intellectual and administrative infrastructure to support the Institute’s initiatives and goals.

Prior to joining the Institute in January of this year, Dr. Hobbs was Executive Associate Dean for Clinical and Translational Research at the University of Arkansas for Medical Sciences (UAMS) and Arkansas Children’s Hospital. In that role, she supported faculty scientists in their mission to develop biomedical knowledge leading to improved healthcare.

At UAMS she held a number of key leadership positions. Until her departure in December 2018, she was also Chief Research Information Officer. During 2016-2017, as a professor in the Department of Pediatrics, she fulfilled the role of director and co-principal investigator of the NIH-funded Data Coordinating and Operations Center for the 17-site Pediatric Clinical Trial Network in 2016-2017. Throughout her career, she continued her clinical service in neonatology attending in Level I to III nurseries.

“I am delighted to be part of the Institute’s pioneering team bringing precision genomic medicine to the cribs and bedsides of critically ill infants and children,” said Dr. Hobbs. “I finished pediatric residency 23 years ago, before the first human genome was sequenced. At that time, it was beyond my wildest imagination that someday I would have the opportunity to bring together my experience and skills in clinical medicine, informatics and genomics to join an extraordinary team combining science and medicine to improve the health of babies and children for generations to come.”

Dr. Hobbs is married to Jim Robbins, PhD, a native of Little Rock, AR and a health service researcher. They have three adult children between the ages of 21 to 23, who are currently in college.

Rady Children’s Launches “Project Baby Bear”

Rady Children’s Launches “Project Baby Bear”

$2 million Medi-Cal pilot funded by the State of California to provide genomic testing to acutely ill newborns in select cities across California

Sept. 26, 2018—Rady Children’s Hospital-San Diego is launching Project Baby Bear, the first California State funded program to offer rapid whole genome sequencing (WGS) for critically-ill newborns.

The $2-million Medi-Cal pilot program will provide genome testing for babies hospitalized in intensive care. Project Baby Bear will leverage rapid WGS as a first-line diagnostic test done by Rady Children’s Institute for Genomic Medicine for babies at four participating hospitals statewide.

“We are honored to be selected as the first California children’s hospital to use the Medi-Cal platform to deliver access to this life-changing test to children who need it, regardless of their family’s ability to pay,” said Donald Kearns, MD, MMM, President and CEO of Rady Children’s. “California is once again leading the way in improving the lives of children and families with Project Baby Bear.”

Whole genome sequencing has been used at Rady Children’s to diagnose babies and children hospitalized in intensive care with rare diseases since July 2016, but only as part of clinical trials. As of Sept. 20, the Institute has sequenced nearly 1,200 children. More than one-third (34 percent) received a genomic diagnosis enabling physicians to make life-changing adjustments in care for 70 percent of those diagnosed.

Until the initiation of Project Baby Bear, whole genome sequencing has not been covered by insurance or Medi-Cal and was available only through clinical trials paid for by research grants or philanthropic donations.

At the launch announcement held today (Sept. 26) at Rady Children’s, Stephen Kingsmore, MD, DSc, President and CEO of Rady Children’s Institute for Genomic Medicine, introduced a mother whose newborn received a life-saving diagnosing through genomic sequencing.

Kara Coltrin shared the story of how her son suffered unrelenting seizures that took him to the brink of death before WGS pinpointed the cause of his illness and led doctors to change his treatment. “Genomic testing saved his life,” she said. “We’re blessed to be able to share his story so that we can help other children have access and give their parents hope.”

The Rady Children’s Institute for Genomic Medicine team led by Kingsmore holds the world record for fastest diagnosis through genomic sequencing at 19.5 hours. “Here at Rady Children’s, we’ve seen that using whole genome sequencing to diagnose and guide the care of babies hospitalized with rare diseases is reducing suffering and infant mortality, decreasing hospital stays and healthcare costs,” Kingsmore said.

“We are enormously grateful to the leadership of our elected officials in California for their willingness to support this important demonstration project,” Kingsmore added. “It’s our belief that rapid whole genome sequencing should become a first-line diagnostic test and standard of care in neonatal intensive care units everywhere.”

The program was championed by the California Legislative Rare Disease Caucus co-chaired by Assemblyman Brian Maienschein. He was among the lawmakers on hand for the program launch at Rady Children’s Hospital. Also attending was State Senate President Pro Tem Toni Atkins, Assemblyman Todd Gloria and State Secretary of the California Health and Human Services Agency Michael Wilkening.

Whole Genome and Exome Sequencing are Superior Diagnostic Tests for Children with Suspected Genetic Diseases

First meta-analysis of scientific literature underscores the greater clinical and diagnostic utility of sequencing compared to standard genetic testing

July 9, 2018–Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) of children with suspected genetic diseases are more useful than the current first-line test, according to a study published today by the Rady Children’s Institute of Genomic Medicine in the journal npj Genomic Medicine.

The study compared the usefulness of the current most established testing method—
chromosomal microarray (CMA)—to relatively new, more advanced tests: WGS and WES—in detecting the cause of genetic anomalies and guiding medical management of patients.

“What we learned is that WGS and WES offer greater diagnostic and clinical utility than CMA, leading us to conclude that WGS and WES should be considered first-line genomic tests for children with suspected genetic diseases,” said Michelle Clark, PhD, statistical scientist at the Rady Children’s Institute of Genomic Medicine (RCIGM) and the first author of the study.

Genetic diseases are the leading cause of death in infants in North America affecting an estimated four percent of newborns. Rare genetic diseases also account for approximately 15 percent of admissions to children’s hospitals.

Since 2011, Whole Genome and Whole Exome sequencing have been increasingly used for diagnosis of genetic diseases, primarily on an experimental basis as guidelines do not yet exist for their use. In addition, medical insurance reimbursement for is available on a very limited basis for WES but not for WGS. As a consequence, while these tests are more useful, they are not widely available.

The basis for the publication was a thorough, systematic review of scientific literature covering nearly seven years (January 2011 to August 2017). The study, led by RCIGM president and CEO Stephen Kingsmore MD, DSc, analyzed the results of 37 research studies involving more than 20,000 children with suspected diseases and compared the diagnostic and clinical utility of WGS, WES and CMA in these cases.

The Institute team has engineered a Whole Genome Sequencing process to rapidly decode, analyze and interpret the cause of genetic disorders in newborns and children in intensive care in a matter of days.

WGS is a single genetic test that can screen a blood sample for thousands of genetic anomalies and quickly identify the root causes of a child’s condition. As part of their research protocols, the RCIGM team is working to equip clinicians with this critical information to facilitate medical decision making.

Most important, early intervention may avoid unnecessary treatment, invasive surgeries, and reduce hospitalization time, ultimately reducing suffering, bringing down the cost of care and improving quality of life for affected babies and children.

“Our hope is that Whole Genome Sequencing will soon become routine so that all children who need it can have access to this life-saving technology,” said Kingsmore.

Currently, RCIGM is offering rapid Whole Genome Sequencing (rWGS) only through research studies offered to patients at Rady Children’s Hospital-San Diego and children’s hospitals participating in RCIGM’s clinical trials. Among the hospitals collaborating with RCIGM are Children’s Hospital of Orange County, Children’s Minnesota, Colorado Children’s and Nicklaus Children’s Hospital (Miami).

WGS Helps Diagnosis and Reduces Healthcare Costs for Neonates in Intensive Care

European Society of Human Genetics Milan, Italy: Children who are born severely ill or who develop serious illness in the first few weeks of life are often difficult to diagnose, with considerable implications for their short and longer-term care. Whole genome sequencing*carried out quickly has the potential to provide an early diagnosis, and thus improve the clinical care of these infants as well as reducing its cost, the annual conference of the European Society of Human Genetics will hear tomorrow (Sunday).

Dr Shareef A. Nahas, Senior Director, Rady Children’s Institute for Genomic Medicine, San Diego, CA, United States, will report on his team’s study of rapid whole genome sequencing (rWGS) of all inpatient children under one year of age who were nominated for genetic investigation at Rady Children’s Hospital. Rapid WGS is able to return results in 48 to 96 hours, whereas standard genetic testing takes six to eight weeks to provide a result. They then noted subsequent changes in medical care that occurred while the child was still in hospital. Where there was a significant change in care due to a new diagnosis, the cases were reviewed by an independent expert panel who tried to determine what they believed would have happened had the child not received rWGS.

After 12 months of testing, 363 patients had been enrolled in the study and rWGS interpreted in 340 of them. This yielded a diagnosis in 115 cases (about 34%). Diagnosis occurred quickly, on average within 96 hours. Changes in management as a result of diagnosis were identified in 77 patients, or about 67% of those diagnosed. Such changes ranged from specific changes, for example surgical interventions, to guidance in palliative care. Among the first 42 infants diagnosed, rWGS provided over $1.3million in net cost saving over the projected standard care.

“To date, our studies have shown a considerable clinical and economic benefit of sequencing children who were identified by clinicians as being suspected of having a genetic disorder. In the course of the study, one child was spared devastating neurological damage,and one had a significantly reduced risk of death. The net cost savings totalled several hundred thousand dollars, even when we included the cost of analysing the genome of the child and both parents, » says Dr Nahas.

Although many studies have shown that WGS improves the diagnosis if genetic disorders in infants and can lead to beneficial changes in their management, the new research has shown that, by implementing rapid sequencing, cost savings will also ensue. « We are now in a situation where we have a technology that leads to improved diagnosis and improved outcomes but is also not a net burden on healthcare resources. This means that for large healthcare payers, there is not a logical cost barrier to implementing rWGS in neonates suspected to have a genetic disorder. There will need to be further data on who else can benefit from early use of this technology but implementation in the current cohort should not be delayed, » says Dr Nahas.

Currently, the use of WGS among sick neonates is very infrequent across the world, and there are few healthcare systems that have the ability to turn round genetic testing quickly enough to be clinically relevant, the researchers say. This is vital if medical management needs to be changed during the childrens’ hospitalisation. In the course of Dr Nahas’ study, one child was spared devastating neurological damage and another had a significantly reduced risk of death.

« The logic for the use of rWGS in these patients, both diagnostic and economic, is totally convincing. We have demonstrated that early sequencing saves money during admission. We were surprised by the proportion of children who received a change in care during that admission – around 25% of children sequenced and 80% of those diagnosed. This rate is much higher than other published rates for neonates who received WGS. We believe that this difference is due to the fact that the children received results at a much younger age, at a point where medical decisions were yet to be made.

« There is an ethical imperative to act in the best interest of neonates, but implentation will require a concerted effort across all healthcare systems, and this will need to be at government level in Europe. Consistent with many diagnostic tests in the post-natal period, rWGS has the potential to identify conditions associated with lifelong disability or shortened lifespans, » Dr Nahas will conclude.

In a second presentation, Courtney French, PhD, a research associate/bioinformatician at the University of Cambridge, Cambridge, UK, will describe how she and colleagues carried out WGS analyses on 145 severely ill babies and children with an unidentifiable disease. As a result, they were able to identify the cause of disease in more than 15% of cases.

« We have developed a rapid, affordable turnaround pipeline for this sequencing within the UK National Health Service system. This means that we can feed back clinically relevant information to doctors and parents in a timescale that allows care to be affected. Because it is hard to tell from observation alone who will benefit from genomic diagnosis, we think that it should be carried out on all eligible children, rather than doctors deciding on individual cases based on previous clinical knowledge. By comparing the entire DNA sequence in children to that of their parents we can identify quickly the likely cause of disease, » says Dr French.

The researchers are using their current data to investigate how rare genetic diseases present at an earlier stage than they are usually diagnosed in newborns. « Greater numbers of patients will expand our ability to do this, and we hope that our work will serve as a model for expanding the programme to other hospitals and regions, » Dr French will say. « The success of this project will depend on people working together across the health research and healthcare system. The translation of this work to routine care will require significant investment of resources in achieving consent from parents, and in giving information at what is a very stressful time for them. »

Many of the conditions characterised through WGS to date can be treated more effectively once identified. In the Cambridge dataset, several epilepsies that respond better to some medications than others were found. And there were cases where the diagnosis was able to prompt better screening for the clinical consequences of a condition and enabled the creation of a properly focused care plan, for example cardiac surveillance, renal follow up, or dietary advice. Even where there is no effective treatment available, having a diagnosis can provide reassurance to families that all that could be done has been done, and it can also provide useful information to parents when they are considering the most appropriate care for their child in the future.

« We were pleasantly surprised at the enthusiastic welcome parents gave to our study, with more than half of those approached wanting to take part. Despite the complications of getting samples from both parents, as well as their child, we managed to achieve this in 85% of families. We were also surprised at the huge range of clinical conditions we were able to diagnose, and particularly to find that when a child was already known to have learnng disability or developmental delay we were more likely to make a genetic diagnosis. This reflects the enormous increase in genetic knowledge over the last decade; ten years ago we would not have been able to do this even if we had sequenced the genome.

« Genome sequencing is currently rare in newborns and paediatric cases, but our research has shown that it can be extremely effective in providing rapid answers in difficult to diagnose cases. It is also be cost-effective, since it can reduce the time spent as an in-patient. Early diagnosis of neonatal and paediatric disease is not only important in pointing the way to the best care and treatment, but also in reducing anxiety for parents, » Dr French will conclude.

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University, Newcastle, United Kingdom, said: “Both these studies confirm the value of genome sequencing to detect the cause of unexplained disease. The study of Nahas shows that this can now even be done within four days, which is very impressive. This greatly increases the practical use of genetics in an acute clinical setting where treatment decisions can now be made based upon this powerful test. Personalised genomic medicine is becoming a reality!”

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*. Whole genome sequencing is the process of determining the complete DNA sequence of an individual, including all the chromosomal DNA and that contained in the mitochondria.

Nahas: Abstract no: CO7.5. Rapid Whole Genome Sequencing Improves Clinical Utility and Cost Effectiveness of Acutely Ill Children admitted to Neonatal Intensive Care Units

French: Abstract no: CO7.4 Next Generation Children Project: Whole genome sequencing for rapid diagnosis of severely ill children in intensive care

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