Departments of Anesthesiology and Molecular Physiology & Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
NeuroChlore, Campus Scientifique de Luminy, 163 Route de Luminy, 13273 Marseilles, France.
Cells. 2022 Aug 4;11(15):2419. doi: 10.3390/cells11152419.
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.
特异性 NKCC1 协同转运蛋白拮抗剂布美他尼可减轻自闭症谱系障碍（ASD）和许多神经发育或神经退行性疾病在动物模型和临床试验中的严重程度。然而，NKCC1 在全身许多细胞类型中的普遍表达被认为会挑战布美他尼的治疗效果。然而，许多外周功能，包括肠道、代谢或血管等，在导致神经后遗症的脑部疾病中受到干扰。这些功能的改变也会增加疾病的发病率，表明与临床表现存在复杂的双向联系。我们认为，有必要对 ASD 和其他疾病进行更全面的观察，以解释受原始宫内损伤影响的多个部位。从这个角度来看，中枢和外周作用的广谱活性再定位药物可能是治疗这些疾病的一种有用方法。
