The specific NKCC1 cotransporter antagonist, bumetanide, attenuates the severity of Autism Spectrum Disorders (ASD), and many neurodevelopmental or neurodegenerative disorders in animal models and clinical trials. However, the pervasive expression of NKCC1 in many cell types throughout the body is thought to challenge the therapeutic efficacy of bumetanide. However, many peripheral functions, including intestinal, metabolic, or vascular, etc., are perturbed in brain disorders contributing to the neurological sequels. Alterations of these functions also increase the incidence of the disorder suggesting complex bidirectional links with the clinical manifestations. We suggest that a more holistic view of ASD and other disorders is warranted to account for the multiple sites impacted by the original intra-uterine insult. From this perspective, large-spectrum active repositioned drugs that act centrally and peripherally might constitute a useful approach to treating these disorders.
Keywords: ASD; NKCC1; alzheimer’s disease; blood-brain barrier; brain-gut interactions; bumetanide; central and peripheral actions of bumetanide; clinical trials; immune alterations in brain disorders; neurodevelopmental disorders; parkinson’s disease; side effects.