A NOVEL THERAPY FOR RESPIRATORY SYNCYTIAL VIRUS

描述(申请人提供)：临床上需要一种经济有效、无毒的口服疗法来治疗幼儿和免疫缺陷成人的呼吸道合胞病毒(RSV)感染。MicroBiotix正在开发NMSO3，一种硫化唾液酸脂的易溶钠盐。该化合物是一种有效的RSV抑制剂，在动物模型感染中具有口服和体内非肠道疗效。NMSO3具有抑制呼吸道合胞病毒的特异性。申请人的目标是尽快准备该化合物的扩展生物学概况，以便它可以作为研究性新药(IND)候选申请进行进一步开发。人们建议进行研究，以定义表观的多层次作用机制。这对于将NMSO3发展成为一种有效的治疗药物至关重要。MicroBiotix还将细化治疗棉花大鼠呼吸道合胞病毒肺部感染的最佳剂量方案，并确定在这些剂量条件下的治疗指数。在第二阶段SBIR研究中，MicroBiotix计划制备良好的制造规范(GMP)质量的NMSO3，建立NMSO3在棉花大鼠模型中的基本药代动力学和口服生物利用度以及急性毒性。目标是在第一阶段SBIR研究开始后三年内提交IND。

DESCRIPTION (provided by applicant): There is a clinical need for a cost-effective, non-toxic oral therapy to treat Respiratory Syncytial Virus (RSV) infections in young children and immuno ompromised adults. Microbiotix is developing NMSO3, a readily soluble sodium salt of a sulfated sialic acid-lipid. This compound is a potent RSV inhibitor with both oral and parenteral in vivo efficacy in animal model infections. NMSO3 has shown specificity for inhibition of RSV. It is the applicant's aim to prepare an expanded biological profile of this compound as soon as possible so that it might undergo further development as an Investigational New Drug (IND) application candidate. Studies are proposed to define the apparent multi tiered mechanism of action. This will be essential to the development of NMSO3 as an effective therapeutic drug. Microbiotix will also refine the optimum-dosing regimen for treating RSV lung infections in cotton rats, and define the therapeutic index under those dosing conditions. In the Phase II SBIR studies, Microbiotix plans to prepare good manufacturing practice (GMP) quality NMSO3, establish the essential pharmacokinetics and oral bioavailability and the acute toxicity for NMSO3 in cotton rat model. The goal is to file an IND within three years of initiation of the Phase I SBIR studies.