Using ACT01 - DHA combination to Improve Conditions of FXS

Abstract and Project SummaryFragile X SyndromeFXSis a leading inherit cause of intellectual disabilityThe goal of this project is to develop effective medications to improve conditions of FXSThe proposed research is based on the hypothesis that a combined administration of ACTand DHA to the FmrKO micea mouse model of FXSwill rescue brain developmentThe hypothesis is based on experimental observations that dopaminergic deficit and adrenergic excess are involved in the delayed FmrKO brain developmentACTis a dopamine reuptake specific blocker capable of reversing DA deficitDHA is an nfatty acid reportedly capable of attenuating excessive norepinephrine actionsDA and DHA are required for brain functionsACTand DHA combination should restore catecholaminergic balance and rescue brain developmentThe research will characterize the effects of ACTDHAand their combinationon behaviors and blood and cerebral biochemistriesThe behavior research examines the effects of each agent and their combination behaviors associated with different brain regionsThe blood biochemistry characterizes the effects of ACTDHAand their combination on catecholaminergic regulated lipid and glucose metabolic balancesStudying these metabolic activities as biomarkers is a mean to assess these agentsandapostargetedcatecholaminergic activitiesengagementsThe cerebral biochemistry focuses on examining expression levels of neuronal and astrocytic proteinse gglucose transportersdown stream from respective mTOR pathways of different cellsCatecholamines take part in regulating the balanced expressions of these proteins during brain maturation processCombination of ACTand DHA should help to restored DA NE balanceRestored catecholaminergic homeostasis should rescue behaviornormalize metabolic activitiesand restore the neuronal astrocytic balanceCompletion of these studies will provide a coherent body of proof of concept experimental evidence to support our goal of providing effective therapeutic for FXS Narrative Our research and literature have shown that dopaminergic deficit and adrenergic excess contribute to conditions of Fragile X SyndromeWe propose that a combination of ACTand DHA should benefit Fragile X patients because ACTis capable of reversing dopaminergic deficit and DHA is capable of tempering adrenergic excessThe proposed research aims to provide proof of concept experimental evidence