Crosslink augmentation to resist snoring and obstructive sleep apnea syndrome

描述(申请人提供)：打鼾症是一种影响所有年龄段的人的疾病，据报道，男性的患病率高达48%，女性的患病率高达34%。打鼾症不仅会扰乱患者床伴和家庭的睡眠周期，还可能导致患者睡眠不足，并导致更严重、有时危及生命的阻塞性睡眠呼吸暂停综合征(OSAS)，即睡眠时呼吸因呼吸道物理阻塞而中断。据估计，美国16岁及以上人群中OSAS的患病率为4.2%，约为1000万人。打鼾症和阻塞性睡眠呼吸暂停综合征在大多数情况下都是由于呼吸道几何形状异常和软腭有异常变形倾向而导致气流受阻的结果。由于打鼾会反复损伤软腭部，预计会增加其被动变形能力，并损伤肌肉纤维和周围神经纤维，增加阻塞的倾向。因此，鼾症的治疗在降低OSAS的发生率方面可以发挥重要作用。目前的治疗方法包括手术、使用口腔矫治器，以及最近针对软腭僵硬的微创手术。所有较新的手术都在一定程度上依赖于纤维瘢痕组织的形成来使软腭僵硬。 这种纤维化组织可能会表现出较差的机械性能和结构完整性的丧失，导致最终失去一些与最初治疗相关的好处。这 第一阶段研究旨在确定注射无毒蛋白质交联剂的可行性，以在不产生疤痕组织的情况下使软腭僵硬。先前的测试表明，这项技术可以增强软腭的机械性能，减少振动，同时增加对机械降解的抵抗力。这一计划的总体目标将是将一种更便宜、更快(当天受益)和卓越的注射疗法商业化，以减少鼾症、预防OSAS和减少呼吸道塌陷。可行性将分四个部分进行评估：1)将测试交联剂改善软腭组织力学性能和增加其抗机械降解能力的能力；2)将开发风洞测试系统来测量马软腭的振动幅度和振荡频率；3)将使用风洞来量化首选交联剂注射后马软腭的振动减少；ad 4)将在涉及治疗正常马和被诊断为软腭背移位(DDSP)的马的软腭背移位(DDSP)的初步研究中评估安全性和治疗效果。

DESCRIPTION (provided by applicant): Snoring is a condition that affects people of all ages, with a reported prevalence of up to 48% of men and 34% of women. Snoring poses not only an inconvenience with regard to sleep-cycle disruption of the sufferer's bed partner and family, but it can also lead to sleep-deprivation in the sufferer and to a more serious and sometimes life-threatening condition, obstructive sleep apnea syndrome (OSAS), where breathing is interrupted during sleep by physical obstruction of the airway. Prevalence of OSAS in the United States has been estimated at 4.2% for those aged 16 and older, or approximately 10 million individuals. Both snoring and OSAS are in most cases the result of obstructed airflow due to abnormalities in the geometry of the air passages and the propensity for aberrant deformation of the soft palate. Repeated trauma to the soft palate due to snoring can be expected to increase its passive deformability and damage muscle fibers and peripheral nerve fibers, increasing the tendency for obstruction. Thus, treatment of snoring can play an important role in reducing the incidence of OSAS. Current treatments include surgery, the use of oral appliances, and more recently, minimally invasive procedures targeted at stiffening the soft palate. All of the newer procedures rely to some extent on the formation of fibrotic scar tissue to stiffen the soft palate. This fibrotic tissue can be expected to exhibit inferior mechanical properties and loss of structural integrity, leading to the eventual loss of some initial treatment-related benefits. This Phase I study aims to determine feasibility of injecting non-toxic protein crosslinking agents to stiffen the soft palate without producing scar tissue. Previous testing suggests that this technique can augment the soft palate's mechanical properties, reduce vibration, and concomitantly increase resistance to mechanical degradation. The overall aim of this program will be to commercialize a less expensive, faster (same-day benefit), and superior injectable treatment for the reduction of snoring, prevention of OSAS, and reduction of airway collapse. Feasibility will be evaluated in four parts: 1) the ability of crosslinking agents to improve the mechanical properties and increase the resistance to mechanical degradation of soft palate tissue will be tested; 2) a wind tunnel test system will be developed to measure the vibration magnitude and oscillation frequency of horse soft palates; 3) the wind tunnel will be used to quantify reduction of vibration in horse soft palates following preferred crosslinker injections; ad 4) safety and treatment effect will be evaluated in pilot studies involving treatment of soft palats in normal horses and horses diagnosed with dorsal displacement of the soft palate (DDSP) which involves a form of awake snoring and apnea.