Channel Replacement Therapy for Cystic Fibrosis

描述（申请人摘要）：机舱的总体目标是开发 并商业化一种上级囊性纤维化（CF）治疗剂， 一个独特的肽家族，将在缺陷的细胞中形成功能性离子通道。 细胞膜Nacelle Therapeutics将这种治疗方式称为 “基于肽的通道替代疗法。“预计， 跨膜离子流将消除或减少炎症的发生， 粘液形成和感染，并将导致大大减少需要 用于目前使用的抗炎和抗感染产品。的 对气道清除治疗的需要也将减少。具体目标 第一阶段研发的目的是评估体液效应或重复暴露于 将小鼠注射到临床剂量的铅舱CF的所有L-或D-同种型 治疗性通道形成肽。然后将对经治疗的小鼠进行评价 用于肽诱导的免疫或炎症反应。具体 第一阶段的评估包括物理、电生理和生物 在CF小鼠模型中测试测试化合物的有效剂量， 以及免疫原性和炎症反应的激活， 野生型小鼠和培养细胞的上皮和肺泡巨噬细胞。 拟议的商业应用：成功将导致广泛使用的CF治疗。 由于有缺陷的离子通道越来越多地与各种人类疾病（发作性共济失调，糖尿病，癫痫和阿尔茨海默氏痴呆症）有关，因此基础技术可能会产生更广泛的影响。 在离子交换和电池中的非医疗、改性膜应用也是可以实现的。

DESCRIPTION (Applicant's abstract): Nacelle's overall objective is to develop and commercialize a superior cystic fibrosis (CF) therapeutic, derived from a family of unique peptides that will form functional ion channels in defective cell membranes. Nacelle Therapeutics refers to this treatment modality as "Peptide-based channel replacement therapy." It is anticipated that enhanced transmembrane ion flow will eliminate or reduce the incidence of inflammation, mucous formation, and infection, and will result in a greatly diminished need for the currently employed anti-inflammatory and anti-infective products. The need for airway clearance therapies will also be diminished. The specific goal of the Phase I R/R&D is to evaluate the humoral effects or repeated exposure of mice to clinical dosages of both the all L- or D-isoforms of a lead Nacelle CF therapeutic channel-forming peptide. The treated mice will then be evaluated for peptide induced immunological or inflammatory responses. Specific evaluations in Phase I include physical, electrophysiological, and biological testing for effective dosage of the test compounds in the CF mouse model as well as for immunogenicity and activation of the inflammatory response in epithelium and alveolar macrophage of wild type mice and cultured cells. PROPOSED COMMERCIAL APPLICATION: Success will result in a widely used CF therapeutic. Since defective ion channels are becoming increasingly implicated in a variety of human diseases (episodic ataxia, diabetes, epilepsy, and Alzheimer's dementia), the basic technology may have much broader impact. Non-medical, modified-membrane applications in ion exchange and batteries may also be achievable.