SBIR Phase I: A Novel Approach to Cholesteatoma Treatment

这个小型企业创新研究(SBIR)第一阶段项目将开发第一个非手术治疗胆脂瘤的方法。胆脂瘤是一种先天性或获得性的颞骨病变，主要影响中耳和乳突。这些病变具有极强的破坏性，可导致耳聋、头晕、面神经瘫痪、脑脓肿、脑膜炎和死亡。胆脂瘤在世界范围内造成严重的发病率和死亡率。目前，胆脂瘤没有治愈方法，但昂贵的手术超出了大多数发展中国家人口的承受能力。该项目旨在改变人类耳朵中一种天然的机会性病原体的细胞毒性武器库，以摧毁这种疾病。细胞毒作用将由细菌注射体介导，这是一种自然结构，可以将毒素从细菌转移到附着的宿主细胞。在任何时候，治疗都可能被标准抗生素的治疗中断，因为这项技术将通过基因设计对多种抗生素敏感。这一项目的更广泛影响适用于世界上与慢性阻塞性肺病相关的发病率和死亡率的很大一部分人，他们无法获得这种肿瘤的适当治疗。在美国，对于农村和贫困地区来说，胆脂瘤尤其是一个挑战。在发展中国家，这些损害的发生率要大得多，因为它与获得高级医疗保健的机会有缺陷有关。我们工作的最终结果将是一种治疗胆脂瘤的新疗法，它将用一种具有成本竞争力的门诊微创治疗方法取代昂贵的手术。在胆脂瘤的治疗中，迫切需要新的、简单的、负担得起的方法。拟议的实验将为使用细菌机器人开发一种新的治疗方法提供第一步，这种治疗方法将显著改善胆脂瘤的管理，并最终可能以目前成本的一小部分提供完全治愈。如果成功，这种方法可能会被推广并应用于其他恶性上皮生长。

This Small Business Innovation Research (SBIR) Phase I Project will develop the first non-surgical cure for cholesteatoma. Cholesteatomas are congenital or acquired lesions of the temporal bone that primarily affect the middle ear and mastoid. These lesions are highly destructive and can cause deafness, dizziness, facial nerve paralysis, brain abscess, meningitis, and death. Cholesteatomas cause significant morbidity and mortality worldwide. Currently, there is no cure for cholesteatoma but a costly surgery outside the reach of most of the developing world population. The project is aimed at redirecting the cytotoxic arsenal of a natural opportunistic pathogen of the human ear to destroy the disease. The cytotoxic effects will be mediated by the bacterial injectosome, a natural structure that can translocate toxins from the bacterium to the attached host cells. At any time treatment can be interrupted by treatment with standard antibiotics, since the technology will be sensitive to multiple antibiotics by genetic design. The broader impact of this project applies to a large portion of the world population that suffers from morbidity and mortality related to CHST lacks access to adequate treatment of this neoplasm. In the US, cholesteatoma is especially a challenge for rural and indigent regions. In developing countries the incidence of these lesions is much larger, since it is related to defective access to advance medical care. The ultimate end result of our work will be a novel therapy for cholesteatoma that will replace a costly surgery with an out-patient, minimally invasive and cost competitive treatment. There is an urgent need for new, simple, and affordable approaches in cholesteatoma treatment. The proposed experiments will provide a first step in the development of a novel treatment using bacterial robots that will significantly improve cholesteatoma management, and ultimately could provide a complete cure at a fraction of the current cost. If successful, this approach could be extended and applied to other malignant epithelial growths.