Rady Children's Hospital-San Diego

Spina bifida is the most common structural disorder of the human nervous system. The causes are largely unknown, but a new study points to a link involving a chromosomal microdeletion -- and also underscores the value of folic acid as a preventive measure. A group of researchers at the University of California San Diego School of Medicine led an investigation that offers new insight into the causes of spina bifida, the most common structural disorder of the human nervous system. Work of the group, led by Keng Ioi Vong, Ph.D., and Sangmoon Lee, M.D. Ph.D., both from the laboratory of Joseph G. Gleeson, M.D., at the UC San Diego School of Medicine Department of Neurosciences and the Rady Children's Institute for Genomic Medicine, reveals the first link between spina bifida and a common chromosomal microdeletion in humans. The study demonstrates that individuals carrying this chromosomal deletion -- present in one of 2,500 live births -- demonstrate a risk of spina bifida more than 10 times greater than the general public. The study also underscores the potential role of a common food supplement in reducing the risk of spina bifida. The findings were recently published in the journal Science. Gleeson, Rady Professor in the Department of Neuroscience and director of neuroscience at Rady Children's Institute for Genomic Medicine, is the senior author of the study. He explained that spina bifida, also known as meningomyelocele, affects one in every 3,000 newborns. Unfortunately, the causes are mostly unknown. A few mutations were reported but could only explain a tiny fraction of risk, Gleeson added. To uncover the genetic causes of the disease, Gleeson's UC San Diego lab joined with colleagues from across the globe to establish the Spina Bifida Sequencing Consortium in 2015. The consortium began focusing on a tiny deletion in chromosome 22. Chromosome microdeletions refer to a condition in which several genes in a chromosome are missing. The group's target condition, known as 22q11.2del, has been implicated in a number of other disorders. They began looking for 22q11.2del in spinal bifida patients. "All patients we recruited have the most severe form of spina bifida, and all underwent best-practice comprehensive genomic sequencing," Gleeson said. "We identified 22q11.2del in 6 out of 715 patients. This may not seem a high percentage, but this is by far the most common single genetic variation that could contribute to spina bifida." He went on to say the group identified eight additional spina bifida patients who carried the deletion from a cohort of approximately 1,500 individuals recruited because of the presence of the common 22q11.2 deletion, Gleeson said. The researchers then narrowed the cause among the many genes in the 22q11.2 deletion to a single gene known as CRKL. Gleeson explained that there are nine other genes in this chromosomal region that could have been the cause. He said the team began a process of elimination, "knocking out" each of the mouse genes one-by-one, when they received a fortuitous email from Dolores Lamb from Weil Cornell College of Medicine. Lamb had noted some of the mice in their vivarium that were missing Crkl and showed spina bifida. (Vong explained that researchers use all capital letters to describe the gene in humans, and lower-case for mice. )Lamb's group heard about the Gleeson lab project throughs the Spina Bifida Association. "This finding really got us excited because it meant that CRKL disruption might be sufficient for spina bifida," said Vong, co-first author of the study. "We removed the mouse Crkl gene ourselves and confirmed that some of the mice developed neural tube defects, including spina bifida." Most of the other genes in 22q11.2 deletion were subsequently excluded, he added. They next turned their attention to how folic acid may modulate CRKL-mediated spina bifida. Vong noted that prior studies in humans demonstrated that folic acid (also known as vitamin B-9) supplementation prior to conception reduces the incidence of spina bifida and other neural tube defects by up to 30-50 percent, but the mechanisms are still a mystery. "When we deprived the Crkl mutant female mice of folic acid in their chow, many more of their offspring had neural tube defects, and the severity increased dramatically," Vong explained. "This suggests that folic acid taken by pregnant women may not only reduce the risk, but also the severity of neural tube defects in their offspring." "We hope our findings can help the research community to better understand causes of neural tube defects, especially the causes attributable to common genetic findings like 22q11.2 deletion," Gleeson said. "We also hope our findings can contribute to healthy pregnancies, improved women's health, and improved outcomes for children." Co-authors associated with the University of San Diego School of Medicine Department of Neurosciences, as well as with Rady Children's Institute for Genomic Medicine, (in addition to Joseph G. Gleeson Sangmoon Lee and Keng Ioi Vong) are: Renee George, Bryn Gerding, Kiely N. James, Valentina Stanley, Nan Jiang, Kameron Alu, Naomi Meave, Fiza Jiwani, Isaac Tang, Ashna Nisal, Ishani Jhamb, Arzoo Patel, Aakash Patel, Jennifer McEvoy-Venneri, Chelsea Barrows, Celina Shen, Yoo-Jin Ha and Robyn Howarth. Other co-authors include Hal S. Meltzer, of the University of California San Diego Rady Children's Hospital Department of Neurosurgery; Anna S. Nidhiry, of Rady Children's Institute for Genomic Medicine; and the Spina Bifida Sequencing Consortium. This work was supported by the Center for Inherited Disease Research grant HHSN268201700006I, the Yale Center for Genomic Analysis, the Broad Institute, the UC Irvine Genomics Core, the UCSD Institute for Genomic Medicine, the UCSD Transgenic Core, UCSD Microscopy Core grant P30 NS047101, and Columbia Microscopy Core grant S10 OD032447- 01. Other support came from the National Institutes of Health, including National Institute of Diabetes and Digestive and Kidney Diseases, and by support from the Howard Hughes Medical Institute and Rady's Children Institute for Genomic Medicine to Joseph G. Gleeson.

SAN DIEGO, May 7, 2024 /PRNewswire/ -- Rady Children's Hospital-San Diego, one of the nation's top 10 pediatric health care systems, and the University of California San Diego are pleased to announce that Vijay A. Patel, MD, has been appointed as Director of the Pediatric Complex Sinus and Skull Base Surgery Program at Rady Children's Hospital and assistant professor of otolaryngology at UC San Diego School of Medicine. Continue Reading "Dr. Patel is a leader in his field and fits perfectly with the team we've assembled at Rady Children's." Post this Vijay A. Patel, MD Dr. Patel will lead a multidisciplinary team of physicians committed to providing comprehensive care for pediatric patients with complex sinonasal and skull base lesions. Dr. Patel is the only dual fellowship-trained rhinologist and pediatric otolaryngologist on the West Coast, making him acutely prepared to function as a surgical leader and educator for physicians at Rady Children's and UC San Diego School of Medicine. Alongside his clinical work, Dr. Patel has published more than 75 peer-reviewed articles and delivered more than 60 regional and national presentations in otolaryngology, and he is active across several professional networks worldwide. "Dr. Patel is a leader in his field and fits perfectly with the team we've assembled at Rady Children's," says Matthew Brigger, MD, Chief of the Division of Otolaryngology and Director of the Aerodigestive Program at Rady Children's Hospital-San Diego and Professor of Otolaryngology at UC San Diego School of Medicine. "His accomplishments speak for themselves; his hard work, clinical excellence, and ability to lead make him the ideal individual to build this program. We are proud to offer cutting-edge treatments for patients with sinonasal and skull base lesions and even prouder to have Dr. Patel at the forefront of these efforts." Traditionally, complex sinonasal and skull base pathologies in children have been notoriously difficult to treat. However, new advancements in medical technology and surgical techniques now provide patients minimally invasive and scarless options that greatly improve outcomes. At Rady Children's, the Pediatric Complex Sinus and Skull Base Surgery Program offers an endoscopic endonasal approach that removes or alleviates the source of the problem while minimizing damage to surrounding critical structures. These treatments offer several advantages, including avoidance of external incisions, rapid recovery times, a shorter length of hospital stay, and more. "We're thrilled to be working so closely with Dr. Patel. His expertise and dedication bring invaluable contributions to our efforts in advancing pediatric neurosurgery," says Michael Levy, MD, PhD, Chief of Pediatric Neurosurgery at Rady Children's and clinical professor of neurological surgery at UC San Diego School of Medicine. "Dr. Patel's expertise positions us to lead the way in pioneering innovative techniques, especially in complex skull base surgeries such as endoscopic transnasal procedures. This groundbreaking approach to care is transformative for children, as these procedures are rare and not widely performed elsewhere." Dr. Patel attended the University of California Los Angeles for his undergraduate degree in Microbiology, Immunology, and Molecular Genetics with Honors Collegium. He completed medical school at Penn State College of Medicine and performed his surgical training in Otolaryngology - Head and Neck Surgery at Penn State Health Milton S. Hershey Medical Center. He then completed a one-year fellowship in Rhinology and Cranial Base Surgery at the University of Pittsburgh Medical Center and a one-year fellowship in Complex Pediatric Otolaryngology at Children's Hospital Los Angeles. "Rady Children's Hospital-San Diego and UC San Diego have long set the standard for pediatric health care on the West Coast and beyond," said Dr. Patel. "With this new program, we're continuing that legacy in a fundamentally important way, providing children with sinus and skull base conditions with new, minimally invasive options and excellent, long-term outcomes. It's imperative that we increase access to these treatments and train the next generation of clinicians and I couldn't be more thrilled to lead these efforts at Rady Children's." Media contact: Carlos Delgado [email protected] SOURCE Rady Children's Hospital-San Diego

CARLSBAD, Calif., April 26, 2024 (GLOBE NEWSWIRE) -- Exagen Inc. (Nasdaq: XGN), a leading provider of autoimmune testing solutions, today announced changes to the Board of Directors. Exagen is pleased to announce Scott Kahn, Ph.D. is joining the Board as a Class I Director. Dr. Kahn has a distinguished career in life sciences spending over 30 years in global leadership positions. Prior to starting his career in the life science industry, he was an assistant professor of organic chemistry at the University of Illinois. He spent over 10 years at the scientific software company, Accelrys, where he held several positions with increasing responsibility including SVP, General Manager and Chief Science Officer. He then joined Illumina as its first Chief Information Officer and spent 12 years with the sequencing leader. He was most recently with LunaPBC as the Chief Information and Privacy Officer. Dr. Kahn currently holds Board positions at Blue Circle Health, Rady Children’s Institute for Genomic Medicine and Rady Children's Hospital. Dr. Kahn received a B.S. in Chemistry from Rider College, a Ph.D. in Theoretical Organic Chemistry from the University of California, Irvine and was a Fellow Commoner at Churchill College and Postdoctoral Fellow at the University of Cambridge, England. "I am thrilled to join Exagen’s Board of Directors. The management team and the board have made extensive changes over the past year and a half to position the company for a prosperous future. As the company continues its transition, I am eager to contribute to this next phase of growth and innovation," said Dr. Kahn. Additionally, in an ever-continuing effort to streamline operations at the company, Exagen announced that it is reducing the size of the Board of Directors from nine to seven, a change that has been carefully planned and complements our long-term strategy. Brian Birk, Ebetuel Pallares, Ph.D. and Wendy Johnson have all agreed to step down from the Board of Directors, effective on the date of the annual shareholder meeting on June 10th, 2024. “First, I want to thank Brian Birk, Beto Pallares, Ph.D. and Wendy Johnson for their years of commitment and service to the Exagen Board of Directors. They have been instrumental in providing guidance and strategy to the company throughout its growth. Since I joined the company in late 2022, they have been integral in making the necessary changes to focus on achieving profitability and have been extremely supportive throughout my transition,” said John Aballi, President and Chief Executive Officer of Exagen. “As the company evolves, so do the requirements of our Board. To ensure we are well-equipped to grow with these changes, we have appointed Dr. Kahn to our Board of Directors. This is a very exciting time for Exagen as the company enhances its product capabilities, and Dr. Kahn’s expertise will play an important role in this process.” About Exagen: Exagen is a leading provider of autoimmune testing and its purpose as an organization is to provide clarity in autoimmune disease decision making with the goal of improving patients’ clinical outcomes. Exagen is located in San Diego County, California. For more information, please visit Exagen.com or follow @ExagenInc on X (formerly known as Twitter). Forward Looking Statements Exagen cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on Exagen’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: Exagen’s goals, strategies and ambitions; potential future financial and business performance; the potential utility and effectiveness of Exagen’s services and testing solutions; the expected benefits of Dr. Kahn’s position with Exagen; potential shareholder value and growth and 2024 guidance. The inclusion of forward-looking statements should not be regarded as a representation by Exagen that any of its plans will be achieved. Actual results may differ from those set forth in this press release due to the risks and uncertainties inherent in Exagen’s business, including, without limitation: delays in reimbursement and coverage decisions from Medicare and third-party payors and in interactions with regulatory authorities, and delays in ongoing and planned clinical trials involving its tests; Exagen’s commercial success depends upon attaining and maintaining significant market acceptance of its testing products among rheumatologists, patients, third-party payors and others in the medical community; Exagen’s ability to successfully execute on its business strategies; third-party payors not providing coverage and adequate reimbursement for Exagen’s testing products, including Exagen’s ability to collect on funds due; Exagen’s ability to obtain and maintain intellectual property protection for its testing products; regulatory developments affecting Exagen’s business; and other risks described in Exagen’s prior press releases and Exagen’s filings with the Securities and Exchange Commission (“SEC”), including under the heading “Risk Factors” in Exagen’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 18, 2024 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Exagen undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contact: Ryan Douglas Exagen Inc. ir@exagen.com 760.560.1525