inositol / NICHD Neonatal Research Network, National Eye Institute - LARVOL DELTA

Age-Dependent Histone Deacetylase 3 Regulation by βA3/A1-Crystallin and Inositol Hexaphosphate in Retinal Pigmented Epithelial Cells Reveals a Novel Pathway in Age-Related Macular Degeneration. (PubMed, Aging Cell) - "Interestingly, although Cryba1 is not identified as an AMD-linked variant in current GWAS, its loss may be linked to AMD mechanisms. These findings underscore the potential of gene-agnostic and epigenetic therapeutic strategies for treating AMD."

Journal • Age-related Macular Degeneration • Dry Age-related Macular Degeneration • Gene Therapies • Macular Degeneration • Ophthalmology • Retinal Disorders • HDAC3

Neuritin knockout leads to retinal ganglion cell dysfunction (ARVO 2025) - "Purpose Neuritin (Nrn1) is an extracellular glycosylphosphatidylinositol-anchored protein that has been shown to be involved in neuritogenesis and neuronal regeneration following an optic nerve crush injury...Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • NRN1

GM1 Gangliosidosis Type II: Results of a 10-Year Prospective Study. (PubMed, Genet Med) - "Serial phenotyping of type II GM1 patients expands the understanding of disease progression and clarifies common misconceptions about type II patients; these are pivotal steps toward more timely diagnosis and better supportive care. The data amassed through this 10-year effort will serve as a robust comparator for ongoing and future therapeutic trials."

Journal • CNS Disorders • Genetic Disorders • Lysosomal Storage Diseases • Metabolic Disorders • Rare Diseases

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years. (PubMed, Pediatr Res) - P3 | "This study addresses a gap in the literature regarding the relationship between milder forms of retinopathy of prematurity (ROP) that regress without intervention and neurodevelopment and vision outcomes. Children with a history of ROP stage ≤3 without intervention have similar neurodevelopmental outcomes at 2 years' corrected age as children born extremely preterm without a history of ROP and better outcomes than children with a history of ROP with ophthalmologic intervention. Counseling about likely neurodevelopment and vision outcomes for children born extremely preterm with a history of ROP may be tailored based on the severity of ROP."

Journal • Ophthalmology • Retinal Disorders • Retinopathy of Prematurity • Strabismus

PI3Kδ coordinates transcriptional, chromatin, and metabolic changes to promote effector CD8 T cells at the expense of central memory. (PubMed, Cell Rep) - "Patients with activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome (APDS) present with sinopulmonary infections, lymphadenopathy, and cytomegalvirus (CMV) and/or Epstein-Barr virus (EBV) viremia, yet why patients fail to clear certain chronic viral infections remains incompletely understood...Strikingly, activated Pik3cd CD8 cells exhibit altered transcriptional and epigenetic circuits characterized by pronounced interleukin-2 (IL-2)/STAT5 signatures and heightened IL-2 responses that prevent differentiation to memory-like cells in IL-15. Our data position PI3Kδ as integrating multiple signaling nodes that promote CD8 T cell effector differentiation, providing insight into phenotypes of patients with APDS."

Journal • Epstein-Barr Virus Infections • Infectious Disease • Respiratory Diseases • CD8 • FASLG • IL15 • IL2 • MYC • PIK3CD • STAT5

βA3/A1-crystallin regulates apical polarity and EGFR endocytosis in retinal pigmented epithelial cells. (PubMed, Commun Biol) - "We found that βA3/A1-crystallin binds to phosphatidylinositol transfer protein (PITPβ) and that βA3/A1-crystallin deficiency diminishes phosphatidylinositol 4,5-biphosphate (PI(4,5)P), thus probably decreasing ezrin phosphorylation, EGFR activation, internalization, and degradation. We propose that βA3/A1-crystallin acquired its RPE function before evolving as a structural element in the lens, and that in the RPE, it modulates the PI(4,5)P pool through PITPβ/PLC signaling axis, coordinates EGFR activation, regulates ezrin phosphorylation and ultimately the cell polarity."

Journal • EGFR • EZR

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial. (PubMed, J Perinatol) - "Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data."

Clinical • Journal • Cerebral Palsy • CNS Disorders • Ophthalmology • Otorhinolaryngology • Retinal Disorders

INS-3: Inositol to Reduce Retinopathy of Prematurity (clinicaltrials.gov) - P3; N=638; Terminated; Sponsor: NICHD Neonatal Research Network; Trial completion date: Apr 2018 ➔ Dec 2016

Trial completion date • Biosimilar • Ophthalmology • Rare Diseases • Retinopathy of Prematurity

INS-3: Inositol to Reduce Retinopathy of Prematurity (clinicaltrials.gov) - P3; N=638; Terminated; Sponsor: NICHD Neonatal Research Network; N=1760 ➔ 638

Enrollment change • Biosimilar • Ophthalmology • Retinopathy of Prematurity