FGFR3 (ACH) / Tyra Biosci - LARVOL DELTA

METTL16 Modulates GPX4 Expression to Regulate Chondrocyte Ferroptosis. (PubMed, Front Biosci (Landmark Ed)) - "Overexpression of METTL16 improved bone growth and alleviated ferroptosis of chondrocytes by increasing m6A modification of GPX4 mRNA and thus GPX4 expression in chondrocytes. The METTL16/GPX4 axis may be a promising therapeutic approach for ACH treatment."

Journal • Genetic Disorders • FGFR3 • GPX4 • IL1B • METTL16

Excess FGFR3 signaling in achondroplasia disrupts turnover of resting zone chondrocytes via CREB signaling. (PubMed, Nat Commun) - "To address this, we aimed to generate knock-in mice (Fgfr3Ach) harboring the achondroplasia mutation (p.Gly380Arg)...Administration of CREB inhibitor 666-15 restores growth plate pathology and bone length. These findings demonstrate that excess FGFR3 signaling disrupts resting zone chondrocyte properties and suggest potential therapeutic targets for achondroplasia."

Journal • Endocrine Disorders • Genetic Disorders • FGFR3

CDK8 inhibitor KY-065 rescues skeletal abnormalities in achondroplasia model mice. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "The first precision drug approved for the treatment of ACH in children, the C-type natriuretic peptide analog vosoritide, antagonizes the MAPK pathway, while there are currently no effective and safe medications targeting the STAT1 pathway. Moreover, daily administration of 10 mg/kg KY-065 to Fgfr3Ach mice (yielding a peak concentration of 22.0 ± 1.47 μM in plasma) resulted in significant elongation of long bone and improved growth plate cytoarchitecture. Collectively, these findings identify the CDK8 in chondrocytes as a potential therapeutic target for ACH and KY-065 as a promising candidate drug treatment for this debilitating skeletal disease."

Journal • Preclinical • Endocrine Disorders • Genetic Disorders • Osteoporosis • Rheumatology • FGFR3

Long-term oral meclozine administration improves survival rate and spinal canal stenosis during postnatal growth in a mouse model of achondroplasia in both sexes. (PubMed, JBMR Plus) - "The 2 mg/kg/d dose of meclozine reduced the rate of spinal paralysis caused by spinal canal stenosis, maintained the growth plate structure, and recovered the bone quality and growth of axial and appendicular skeletons of Fgfr3ach mice in both sexes. Long-term meclozine administration has the potential to ameliorate spinal paralysis and bone growth in patients with ACH."

Journal • Preclinical • Genetic Disorders • Orthopedics • FGFR3

Cell-based screen identifies porphyrins as FGFR3 activity inhibitors with therapeutic potential for achondroplasia and cancer. (PubMed, JCI Insight) - "In an ex vivo culture system, Pa alleviated defective long bone growth in humanized ACH mice (FGFR3ACH mice). Overall, our study presents a novel approach to discovery and validation of plant extracts or drug candidates that target FGFR3 activation. The compounds identified by this approach may have potential applications as therapeutics for FGFR3-associated cancers and skeletal dysplasias."

Journal • Endocrine Disorders • Genetic Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • FGFR3