Zebrafish Screen for Ototoxic and Otoprotective Agents

描述（由申请人提供）：本SBIR旨在开发一种定量的斑马鱼体内毛细胞测定方法，可用于鉴定潜在的耳保护剂。斑马鱼是鉴定耳保护剂的有用动物模型，因为神经肥大毛细胞位于头部和躯干区域的典型位置，在结构和功能上与哺乳动物的内耳毛细胞相似。人类的毛细胞会因感染、衰老、遗传疾病、噪音或药物治疗（包括抗癌药物和抗生素）而受损。药物性耳毒性最终可导致感觉毛细胞死亡，引起听力丧失和前庭功能障碍。虽然助听器对一些听力损失患者有用，但没有有效的治疗方法。目前的治疗策略包括应用生长因子和其他药物来促进细胞存活，以及全身应用药物来防止程序性细胞死亡的激活。提出的斑马鱼试验将促进保护性治疗的发展，以尽量减少耳毒性副作用，并增加当前药物的临床效用。耳毒性疗法、衰老、环境和遗传因素造成的听力损失是一个巨大的医疗需求未得到满足的市场。在美国，听力损失市场目前达到300亿美元，预计在未来几十年将迅速增长。

DESCRIPTION (provided by applicant): This SBIR aims to develop a quantitative in vivo zebrafish hair cell assay that can be used to identify potential otoprotective agents. Zebrafish is a useful animal model for identifying otoprotectants since neuromast hair cells, which are located in stereotypical positions in the head and trunk region, are structurally and functionally similar to the inner ear hair cells in mammals. Human hair cells can be damaged by infection, aging, genetic disease, noise or treatment with drugs, including anti-cancer drugs and antibiotics. Drug-induced ototoxicity can ultimately lead to sensory hair cell death, causing hearing loss and vestibular disorders. Although hearing aids are useful for some patients with hearing loss, there is no effective therapy. Current therapeutic strategies include application of growth factors and other agents to promote cell survival, and systemic application of drugs to prevent activation of programmed cell death. The proposed zebrafish assay will facilitate development of protective treatments to minimize ototoxic side effects and increase the clinical utility of current medications. Hearing loss from ototoxic therapies, aging, environmental and genetic factors, represents a significant market with unmet medical needs. In the United States, the market for hearing loss is currently at $30 billion and is expected to increase rapidly in the next several decades.