Minimum Effective Dose of Clemastine in a Mouse Model of Preterm White Matter Injury.
Elizabeth OdellNora JabassiniBjörn SchniedewindSarah E Pease-RaissiAdam FrymoyerUwe ChristiansAri J GreenJonah R ChanBridget Elaine LaMonica OstremPublished in: bioRxiv : the preprint server for biology (2024)
Preterm white matter injury (PWMI) is the most common cause of brain injury and cerebral palsy in premature neonates.Clemastine, an FDA-approved antihistamine, was recently identified to strongly promote myelination in a mouse model of PWMI and is a possible treatment.The minimum effective dose in neonatal rodents is unknown and is critical for guiding dose selection and balancing efficacy with toxicity in future clinical trials.We identified the minimum effective dose of clemastine and the associated pharmacokinetics in a murine chronic hypoxia model of PWMI, paving the way for a future clinical trial in human neonates.
Keyphrases
- clinical trial
- white matter
- brain injury
- mouse model
- low birth weight
- cerebral palsy
- endothelial cells
- subarachnoid hemorrhage
- multiple sclerosis
- preterm birth
- preterm infants
- oxidative stress
- phase ii
- open label
- randomized controlled trial
- study protocol
- cerebral ischemia
- double blind
- drug induced
- induced pluripotent stem cells
- drug administration