MYO7A

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

MILAN, Italy, Sept. 16, 2024 (GLOBE NEWSWIRE) -- AAVantgarde Bio (AAVantgarde), an Italy-based global biotechnology company, announced that the first subject has been dosed in the LUCE-1 trial, a Phase 1/2 open label clinical trial to assess safety and tolerability of AAVB-081, using the company’s proprietary dual hybrid gene therapy platform to deliver MYO7A protein in subjects with retinitis pigmentosa related to Usher Syndrome Type 1B (USH1B). This dual-AAV technology for large gene delivery comes from the research of Prof. Alberto Auricchio at TIGEM, an international research institute based in Naples that is owned and managed by the Telethon Foundation. AAVantgarde is a spin-off of TIGEM, and has an exclusive license for the AAV-dual technology for inherited retinal diseases. The first subretinal gene therapy procedure in the LUCE-1 study was supervised by Prof. Francesca Simonelli, Head of the Ophthalmology Unit at the University Hospital of Campania “Luigi Vanvitelli” (Naples). This hospital is one of 3 clinical sites for the Phase 1/2 trial. Dr. Simonelli is global Chief Investigator at the University Hospital of Campania “Luigi Vanvitelli” that is the lead dosing site for the LUCE-1 study. “I am delighted to be involved as Principal Investigator in this first-in-human Phase 1/2 clinical study of AAV-081 for patients with retinitis pigmentosa related to USH1B,” said Prof. Simonelli. “Through this innovative program, we aim to revolutionize our approach to understanding and treating these underserved patients. We are poised to generate robust evidence that will not only advance scientific knowledge, but also directly impact patient care.” Dr. Jayashree Sahni, CMO of AAVantgarde said, “It is an honour to work closely with Prof. Simonelli in this first-in-human clinical trial and leverage her great expertise in developing gene therapies for ophthalmology indications, with a goal of bringing this potentially novel therapy to the USH1B patient community as expeditiously as possible.” Prof. Alberto Auricchio, Founder and CSO of AAVantgarde added, “It is very exciting to have our dual hybrid technology finally tested clinically in an ophthalmology indication. I am very hopeful that all these years of research prove their value in helping these patients that have such a high unmet need.” Dr. Natalia Misciattelli, CEO of AAVantgarde added, “We are honoured to have Prof. Simonelli as Principal Investigator for this clinical study aimed at providing hope for USH1B patients that have no therapeutic options to prevent them from losing their sight. Prof. Simonelli is a pioneer in gene therapy in ophthalmology and her extensive experience in this space will be invaluable to the successful development of this novel therapy.” About the AAVB-081 programAAVB-081 is an intra-retinal AAV8-based dual hybrid product targeting MYO7A-associated Usher syndrome (USH1B). AAVantgarde’s dual hybrid platform uses two AAV8 vectors, each containing one half of an expression cassette encoding for the Myo7A gene and works at the cell nucleus level, recombining the two halves of the transgene back into a single one within the cell. This technology translates into an efficient recombination that generates therapeutically meaningful protein levels in animal models. About the LUCE-1 TrialLUCE-1 is a Phase 1/2 multicenter, open-label, dose escalation study investigating safety, tolerability and preliminary efficacy of 3 dose levels of dual AAV8.MYO7A (AAVB-081) administered subretinally in subjects with retinitis pigmentosa associated with Usher Syndrome Type 1B. About Usher syndrome type 1BUsher syndrome type 1B (Usher1B) is an inherited disease that affects the retina and the inner ear. Usher1B is caused by mutations in the MYO7A gene. The therapeutic gene to treat Usher1B is 6.7 kb long and is therefore too large to fit inside a standard AAV vector. Approximately 20,000 patients in the U.S. and E.U. have Usher1B. These children are born deaf, have vestibular dysfunction, and begin to progressively lose vision in their first decade of life. Although there are surgical treatments available to treat deafness in these patients, there are no treatments available to treat progressive vision loss and blindness in these patients. About AAVantgarde BioAAVantgarde Bio is a clinical stage, Italian headquartered, international biotechnology company that has developed two proprietary Adeno-Associated Viral (AAV) vector platforms to address the gene therapy cargo capacity limitations of AAV vectors. The AAVantgarde platforms could be used to deliver large genes to ocular and non-ocular tissues. Co-founded by Professor Alberto Auricchio at TIGEM (Telethon Institute of Genetics and Medicine) in Naples, Italy, and Telethon Foundation, AAVantgarde will initially validate the platform in the clinic in two inherited retinal diseases with clear unmet need. For more information, please visit: www.aavantgarde.com Contact:Julia Wilson - JW CommunicationsPhone: +44 (0) 7818 430877Email: juliawilsonuk@gmail.com

DURHAM, N.C., Jan. 16, 2024 (GLOBE NEWSWIRE) -- Atsena Therapeutics, a clinical-stage gene therapy company focused on bringing the life-changing power of genetic medicine to reverse or prevent blindness, today announced the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease (RPD) designation to ATSN-101, the company’s investigational gene therapy being evaluated in an ongoing Phase I/II clinical trial in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1). The FDA previously granted Regenerative Medicine Advanced Therapy (RMAT) designation and orphan drug designation to ATSN-101 for the treatment of LCA1. RPD designation is granted by the FDA for serious or life-threatening diseases which affect fewer than 200,000 people in the United States and in which the serious or life-threatening manifestations primarily affect individuals less than 18 years of age. If a Biologics License Application for ATSN-101 for the treatment of LCA1 is approved by the FDA, Atsena may be eligible to receive a Priority Review Voucher that can be redeemed to receive a priority review for any subsequent marketing application or may be sold or transferred. “Rare Pediatric Disease designation is a significant milestone for our LCA1 program as we explore options to advance ATSN-101 into a pivotal clinical trial,” said Patrick Ritschel, MBA, Chief Executive Officer of Atsena Therapeutics. “The FDA designations that have been granted to ATSN-101 not only emphasize the tremendous need for a treatment for patients with LCA1, but also the potential for our subretinal gene therapy to be a major advance in reversing pediatric blindness.” Positive 12-month safety and efficacy data from the company’s ongoing Phase I/II clinical trial of ATSN-101 will be presented at the 47th Annual Macula Society Meeting, which is being held February 7-10, 2024, in Palm Springs, CA. ATSN-101 has demonstrated clinically meaningful improvements in vision at the highest dose and is well-tolerated 12 months post-treatment. Details of the presentation are as follows: Title: Twelve-month safety and efficacy of ATSN-101 in patients with Leber congenital amaurosis caused by biallelic mutations in GUCY2D (LCA1) Session: Inherited Retinal Dystrophy I (Treatment Trials) Date and Time: Wednesday, February 7, 2024, 6:04 p.m. PST Presenter: Christine Nichols Kay, MD About GUCY2D-associated Leber congenital amaurosis (LCA1) LCA1 is a monogenic eye disease that disrupts the function of the retina. It is caused by mutations in the GUCY2D gene and results in early and severe vision impairment or blindness. GUCY2D-LCA1 is one of the most common forms of LCA, affecting roughly 20 percent of patients who live with this group of inherited retinal diseases. There are currently no approved treatments for LCA1. About Atsena Therapeutics Atsena Therapeutics is a clinical-stage gene therapy company developing novel treatments for inherited forms of blindness. The company has two clinical-stage programs, ATSN-201 for X-linked retinoschisis (XLRS) and ATSN-101 for GUCY2D-associated Leber congenital amaurosis (LCA1). ATSN-201, which leverages the company’s novel spreading capsid AAV.SPR, is being evaluated in XLRS patients in a Phase I/II clinical trial known as the LIGHTHOUSE study. The company’s additional proprietary asset is ATSN-301, a dual AAV vector-based gene therapy to prevent blindness from MYO7A-associated Usher syndrome (USH1B). Interim safety and efficacy data from the company’s ongoing Phase I/II clinical trial in patients with LCA1 have demonstrated ATSN-101 is well tolerated and clinically meaningful improvements in vision were observed 12 months post-treatment. Founded by ocular gene therapy pioneers Dr. Shannon Boye and Sanford Boye of the University of Florida, Atsena is based in North Carolina’s Research Triangle, an environment rich in gene therapy expertise. For more information, please visit atsenatx.com. Media Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com Business Contact: info@atsenatx.com