A targeted drug for the treatment of inflammation in cystic fibrosis lung disease

 描述(申请人提供)：有待解决的问题：囊性纤维化(CF)是一个全球性的健康问题，影响着全球超过7万人，其中包括约3万美国人。肺病是慢性阻塞性肺疾病患者发病和死亡的主要原因，其特点是呼吸道有强烈的炎症反应。产品和长期目标：Nanometics LLC(Dba PhD Biosciences)(PHD)正在开发一种有针对性的小分子酶抑制剂，用于治疗慢性肺纤维化肺部疾病的炎症。预计这一新方法将是 有助于减轻患者呼吸道的炎症。技术创新：PHD方法是所有其他CF疗法的独特之处，它利用一种具有高度特异性和皮摩尔亲和力的靶向酶抑制剂来阻止内源性代谢物的循环。代谢产物的积累导致强大和持续的抗炎活性。第一阶段假设：这项第一阶段的SBIR将证明PHD酶抑制剂作为口服治疗慢性肺疾病Scnn1b-TG小鼠模型的可行性。在第一阶段SBIR实验中测试的假设是：(1)单次口服剂量将在24小时内缓解≥的炎症；和(2)一次 每日口服剂量的治疗是无毒的，将促进持续的抗炎状态。具体目标：具体目标#1.证明口服剂量的MTDIA在Scn1b-TG小鼠中的药理和浓度依赖效应。第二阶段：第二阶段SBIR研究将进一步确定作用机制和毒性分布。商业应用：PHD方法是一种独特的抗炎治疗方法，作为单一药物或组合方法的一部分，它将为患者提供更广泛的好处。目前的CF药物市场预计到2019年将达到39亿美元。

 DESCRIPTION (provided by applicant): Problem to be Solved: Cystic fibrosis (CF) is a global health issue that affects over 70,000 people worldwide, including ~30,000 Americans. Lung disease, is the primary cause of morbidity and mortality in CF patients, and is characterized by intense inflammatory responses in the airways. The Product and Long-Term Goal: Nanometics LLC (dba PHD Biosciences) (PHD) is developing a targeted small molecule enzyme inhibitor as a therapeutic for inflammation in CF lung disease. It is anticipated that this new approach will be useful to mitigate inflammation in the airways of patients. The Technological Innovation: The PHD approach is unique to all other CF therapeutics, utilizing a targeted enzyme inhibitor with high specificity and picomolar affinity to block recycling of an endogenous metabolite. Metabolite accumulation leads to robust and sustained anti-inflammatory activity. Phase I Hypotheses: This Phase I SBIR will demonstrate the feasibility of the PHD enzyme inhibitor as an oral therapeutic in Scnn1b-Tg mouse models of CF lung disease. The hypotheses tested during Phase I SBIR experiments will be: (1) a single oral dose will ameliorate inflammation for ≥ 24 h; and (2) once daily oral doses of the therapeutic are non-toxic and will promote a continued anti-inflammatory state. Specific Aims: Specific Aim #1. Demonstrate the Pharmacological and Concentration Dependent Effects of Oral Doses of MTDIA in the Scnn1b-Tg Mouse. Phase II: Phase II SBIR studies will further establish the mechanism of action and toxicity profile. Commercial Application: The PHD approach is a unique approach to anti-inflammatory therapy that will provide an extended benefit to patients as a single agent or part of a combinatorial approach. The current CF drug market is predicted to reach $3.9 billion by 2019.