LT-1002 / LTT Bio-Pharma, Chong Kun Dang - LARVOL DELTA

An Adnp frameshift variant disrupts Wnt signalling inducing chromatocytoskeletal defects and autism-related behaviour in male mice. (PubMed, EBioMedicine) - "We generated a disease-relevant heterozygous Adnp mouse model that recapitulates key molecular and behavioural features observed in patients with Helsmoortel-Van der Aa syndrome. Our findings demonstrate a role for Adnp in chromatin regulation and Wnt signalling, coupled to aberrant expression of cytoskeletal components and synaptic dysfunction. This mouse model provides a mechanistic framework linking chromatin dysregulation to autism-related behaviours and represents a valuable platform for future preclinical studies."

Journal • Preclinical • Alzheimer's Disease • Autism Spectrum Disorder • CNS Disorders • Cognitive Disorders • Developmental Disorders • Genetic Disorders • Mental Retardation • Mood Disorders • Psychiatry • ADNP • CAMK2A • DBN1

Blocking SphK/S1P/S1PR1 axis signaling pathway alleviates remifentanil-induced hyperalgesia in rats. (PubMed, Neurosci Lett) - "Prior to receiving remifentanil, rats were injected with SK-1 (a SphK inhibitor); LT1002 (a S1P monoclonal antibody); CYM-5442, FTY720, and TASP0277308（the S1PR1 antagonists); CYM-5478 (a S1PR2 agonist); CAY10444 (a S1PR3 antagonist); Ac-YVAD-CMK (a caspase-1 antagonist); MCC950 (the NOD-like receptor protein 3 (NLRP3) inflammasome antagonist); and N-tert-Butyl-α-phenylnitrone (PBN, a reactive oxygen species (ROS) scavenger). Our findings indicate that the SphK/SIP/S1PR1 axis regulates the expression of NLRP3, Caspase-1, IL-1β, IL-18 and ROS in the spinal dorsal horn to mediate remifentanil-induced hyperalgesia. These findings may contribute to pain and SphK/S1P/S1PR1 axis research positively, and inform the future study of this commonly used analgesic."

Journal • Preclinical • Metabolic Disorders • Neuralgia • Pain • IL18 • IL1B • NLRP3 • S1PR1

Ion Binding Properties of a Naturally Occurring Metalloantibody. (PubMed, Antibodies (Basel)) - "We crystallized and determined the X-ray crystal structure of the LT1009 Fab fragment in 10 mM CaCl and found that it binds two Ca in a manner similar to its antigen-bound state. To test this hypothesis, we engineered, expressed, and purified a Fab fragment consisting of naïve murine germline-encoded light and heavy chain genes from which LT1002 is derived and observed that it binds Ca in solution. We propose that LT1002 is representative of a class of naturally occurring metalloantibodies that are evolutionarily conserved across diverse mammalian genomes."

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