BChE

Findings offer new insights with potential to inform diagnosis and treatment PHILADELPHIA, Oct. 16, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced the results of a new study highlighting significant genetic links in speech and language disorders in children. The findings, published today in the journal Brain, mark the first time that researchers have studied the genetic basis of linguistic differences separately from other conditions. Genetic factors are known to play a role in speech and language disorders, and the researchers hoped their study would bridge a gap in knowledge to better understand this critical area impacting child development. The research was a collaboration between CHOP's Department of Speech-Language Pathology, the Division of Neurology and the Department of Biomedical and Health Informatics (DBHI). "Our findings highlight the intricate relationship between genes and speech and language development," said Jan Magielski, the study's first author and a data scientist within CHOP's Division of Neurology and Department of Biomedical and Health Informatics. "We hope that the novel connections between genetic causes and specific speech and language disorders reported in the study will offer new and innovative possibilities for earlier intervention and personalized treatment plans." In the study, researchers analyzed electronic medical records of more than 52,000 children treated at CHOP to identify and analyze 26 broad speech and language diagnoses. They found that genetic causes play a major role in speech and language disorders, which are diagnosed more frequently in children between the ages of two and five. While conditions like aphasia, characterized by difficulty speaking, and speech apraxia, or trouble making speech movements, were accurately identified, some speech and language disorders were found to be frequently undetected. Most importantly, stuttering is often underreported in medical records. Their innovative data analysis approach allowed researchers to make three crucial observations. First, they found significant variations in the frequency of speech diagnoses, with mixed receptive-expressive language disorder and developmental disorder of speech and language being the most common diagnosis. Second, the authors observed that speech and language disorders have considerable overlap with neurodevelopmental disorders, movement disorders, and epilepsy. Lastly, the researchers noted that distinct speech characteristics can be linked to specific genes and overlap with known neurodevelopmental conditions. The study connected the genes STXBP1, PTEN and CACNA1A with speech and language disorders. Certain variants of STXBP1 were associated with aphasia while variants of the gene MYO7A were linked with delays in speech and language due to hearing loss. Additionally, in a subset of 726 children with whole exome sequencing data, researchers identified rare genetic changes, linking associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9, and UMODL1 with aphasia. "In the future, we anticipate more targeted studies that delve deeper into the genetic landscape of speech disorders," said Joe Donaher, PhD, CCC-SLP, a senior study author and the Research and Academic Program Director at CHOP's Center for Childhood Communication. "Our study results underscore the need for focused investigations, particularly in areas like stuttering, where genetic research has significantly lagged behind other fields." This study was supported by The Hartwell Foundation through an Individual Biomedical Research Award. This study received support from the National Institute for Neurological Disorders and Stroke, and intramural CHOP funds from the Epilepsy NeuroGenetics Initiative (ENGIN). Magielski, et. al. "The clinical and genetic spectrum of paediatric speech and language disorders." Brain. Online October 16, 2024. DOI: 10.1093/brain/awae264. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Kaila M. Revello Children's Hospital of Philadelphia 267-426-6054 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

THURSDAY, May 25, 2023 -- Researchers have found another clue as to why some infants die suddenly in their sleep, and it's related to a faulty chemical receptor in the brainstem. Experts said the findings provide another puzzle piece in understanding the root causes of sudden infant death syndrome (SIDS). By examining autopsied brain tissue, researchers found that a particular chemical receptor was altered in the brain stems of babies who'd died of SIDS, versus infants who'd died of other causes. The receptor, called serotonin 2A/C, is believed to play a key role in helping a sleeping infant wake up and gasp for air in response to oxygen deprivation. "This 2A receptor is very important in arousing them as a defense mechanism," said Robin Haynes , a researcher at Boston Children's Hospital who led the study. She stressed that the underlying biology of SIDS is complex, and no one is saying an abnormal serotonin receptor is the single culprit. It's thought, Haynes said, that there are multiple mechanisms at work, and they may vary from one infant to another. But for at least some infants who succumb to SIDS, dysfunction in this particular brain receptor may be a reason, she noted. "This study is giving us one more piece of information about the intrinsic vulnerability to SIDS," Haynes said. Many people may know SIDS is related to sleeping position and environment — including the fact that tummy sleeping can raise an infant's risk. In 1992, the American Academy of Pediatrics began advising parents to put their babies to sleep on the back, not the tummy. The federal government, meanwhile, launched a "Back to Sleep" campaign to raise public awareness, and by 1998, the national rate of SIDS had dropped by 45%. However, that decline stalled out. All told, about 3,400 infants die suddenly each year in the United States, including roughly 1,400 who die from SIDS, according to the U.S. Centers for Disease Control and Prevention. Many of the other deaths are caused by accidental suffocation or strangulation during sleep. So over the years, experts have been advising additional safe-sleep measures — like putting babies to sleep only in a crib or bassinet with a flat, firm mattress, and keeping the area free of soft bedding, toys and crib bumper pads. Parents should also have their baby sleep in their room, but not in their bed. But SIDS involves more than environmental factors, Haynes said. There have to be underlying biological reasons that certain infants are vulnerable — characteristics that make them unable to respond normally when an environmental stressor, like tummy-sleeping, impairs their breathing. The new study, published May 25 in the Journal of Neuropathology & Experimental Neurology , is the first to look at whether the serotonin 2A/C receptor may be one of those reasons. Haynes and her colleagues studied tissue collected from the San Diego Medical Examiner's Office, related to the deaths of 70 infants. SIDS was the cause in 58 cases, while 12 infants died of other causes. The researchers found that the serotonin receptor was altered in the brain stems of infants who'd died of SIDS. Gail Bagwell is a clinical nurse specialist in neonatology at Nationwide Children's Hospital, in Columbus, Ohio. She said there is a critical period in infant development when SIDS occurs — usually between 2 and 4 months of age, but up to 6 months. It's thought that biological vulnerability and environmental stressors, such as sharing a bed, coming together during that period can lead to SIDS. As for the underlying biology, Bagwell agreed there will likely be no single culprit. She noted that one recent study, for example, found that blood samples from infants who'd died of SIDS showed decreased activity in an enzyme called butyrylcholinesterase, versus infants who'd died of other causes. That enzyme plays a key role in producing a chemical along the brain's "arousal" pathway. Yet another recent study, of siblings of infants who died of SIDS, suggested that genetics puts some babies at increased risk: Those siblings' own risk of SIDS was fourfold higher than average. How all these different findings might fit together, Bagwell said, is unknown for now. Haynes made a similar point. "We're putting together the pieces of the puzzle incrementally," she said. But while only some infants may have underlying vulnerabilities to SIDS, it's critical that all parents and caregivers follow safe-sleeping practices, both experts said. For one, those steps protect infants from accidental suffocation and strangulation, too. For another, there is no way of identifying which infants are particularly vulnerable to SIDS. That might change in the future. Haynes said one of the ultimate goals is to figure out whether there is a "biomarker" — something that can be easily measured in the blood, for example — that shows whether a newborn is at increased risk of SIDS. Sources Robin Haynes, PhD, principal associate, pathology, Boston Children's Hospital, Harvard Medical School, Boston Gail Bagwell, DNP, APRN, CNS, division of neonatology, Nationwide Children's Hospital, Columbus, Ohio Journal of Neuropathology & Experimental Neurology, May 25, 2023, online Posted May 2023

ANNAPOLIS, Md., June 27, 2011 /PRNewswire/ -- PharmAthene, Inc. (NYSE Amex: PIP) announced today that it has achieved an important technical milestone in its recombinant protective antigen (rPA) anthrax vaccine program. PharmAthene has successfully completed initial technology transfer of its manufacturing process for the bulk drug substance of its vaccine candidate, SparVax, at the 100 liter scale to a US-based manufacturing facility at Diosynth RTP. Activities to scale-up production to the final commercial 1,500 liter scale are underway. "Completion of the technology transfer for SparVax to a domestic manufacturer represents a major technical milestone and significant achievement for our program," remarked Dr. Tom Fuerst, Executive Vice President and Chief Scientific Officer. "As part of this transition, our process sciences team was able to optimize the production process for SparVax increasing our bulk drug substance production yield approximately six-fold, further improving the cost effectiveness of our anthrax vaccine for the United States government. We are currently moving forward to complete the implementation of the GMP manufacturing processes and look forward to commencing additional clinical and non-clinical studies of SparVax in the coming months. Importantly, our achievement of this milestone will enable us to pursue additional advanced development funding." Dr. Fuerst continued, "The benefits of rPA-based vaccines are well established, and we believe our program is at the forefront of efforts in this field. Most importantly, our rPA anthrax vaccine program meets a fundamental objective of Project BioShield, which was established to encourage the development and acquisition of newer, modern medical countermeasures that offer potential improvements in cost, convenience, safety and effectiveness for the U.S. government and its citizens." PharmAthene's rPA anthrax vaccine program has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Disease, National Institutes of Health and the Biomedical Advanced Research and Development Authority. About PharmAthene, Inc. PharmAthene was formed to meet the critical needs of the United States and its allies by developing and commercializing medical countermeasures against biological and chemical weapons. PharmAthene's lead product development programs include: SparVax second generation recombinant protective antigen (rPA) anthrax vaccine Valortim® fully human monoclonal antibody for the prevention and treatment of anthrax infection rBChE (recombinant butyrylcholinesterase) a medical countermeasure for nerve agent poisoning by organophosphorous compounds, including nerve agents and pesticides Statement on Cautionary Factors Except for the historical information presented herein, matters discussed may constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to certain risks and uncertainties that could cause actual results to differ materially from any future results, performance or achievements expressed or implied by such statements. Statements that are not historical facts, including statements preceded by, followed by, or that include the words "potential"; "believe"; "anticipate"; "intend"; "plan"; "expect"; "estimate"; "could"; "may"; "should"; "will"; "project"; "potential"; or similar statements are forward-looking statements. PharmAthene disclaims any intent or obligation to update these forward-looking statements other than as required by law. Risks and uncertainties include risk associated with the reliability of the results of the studies relating to human safety and possible adverse effects resulting from the administration of the Company's product candidates, unexpected funding delays and/or reductions or elimination of U.S. government funding for one or more of the Company's development programs, the award of government contracts to our competitors, unforeseen safety issues, challenges related to the development, scale-up, technology transfer, and/or process validation of manufacturing processes for our product candidates, unexpected determinations that these product candidates prove not to be effective and/or capable of being marketed as products, challenges related to the implementation of our NYSE Amex compliance plan, as well as risks detailed from time to time in PharmAthene's Forms 10-K and 10-Q under the caption "Risk Factors" and in its other reports filed with the U.S. Securities and Exchange Commission (the "SEC"). In particular, at this point there can be no assurance that PharmAthene's rPA product candidate will be shown to be safe and effective and approved by regulatory authorities for use in humans. Copies of PharmAthene's public disclosure filings are available from its investor relations department and our website under the investor relations tab at . SOURCE PharmAthene, Inc.