Novel Epigenetic Test for the Treatment and Improvement of Longitudinal Health-Outcomes for Men with Severe Infertility

NIH SBIR快速通道申请：内在生物科学 总结/摘要 标题：治疗和改善纵向健康结局的新型表观遗传学测试 严重不育的男性 39.7全世界有100万男性（占男性人口的1%）患有最严重的男性性行为。 不孕症：非阻塞性无精子症（NOA）。这些人的精液中没有可识别的精子， 极大地限制了她们生育自己孩子的机会。除了不孕不育的心碎，这些 已经发现男性对于许多长期健康状况包括癌症具有高得多的风险， 代谢疾病和神经精神疾病。缺乏精子通常是他们最早的迹象 潜在的慢性病和躯体疾病根据美国医学会的数据， 生殖医学，应始终筛查遗传性疾病（包括克氏综合征 和Y染色体微缺失），并被引导到进一步的遗传咨询，如果有发现。 NOA患者基本上可以采取一种途径来检索精子细胞：睾丸 活检程序。显微解剖睾丸精子提取（mTESE）是最常见的睾丸活检 手术，并通过切开睾丸和识别曲细精管中的区域进行， 可能的精子生产的口袋。然后精子可以从小管中取出并用于受精 一个鸡蛋。mTESE是非常侵入性和昂贵的（约12，000美元的自掏腰包），只有40-50% 找到精子的成功率 为了给这些男人最好的选择怀孕和长期的健康管理， 杨百翰大学（BYU）的Jenkins和Hill实验室与Inherent Biosciences合作 （固有的），正在开发一种新的，单一的综合诊断测试，1）预测mTESE的成功 具有极高的准确性，以指导取精治疗和随后的受孕，2）更准确地 识别所有Y染色体微缺失的亚型（这是一个重要的预后指标），以及3） 确认了克氏综合征被称为NOA-guideTM，这种诊断测试将可供所有 NOA男性（占男性人口的1%）。”“ 精液样品中的精子来源cfDNA，以确定从睾丸中取出的精子是否是可行的。 为诊断为NOA的男性提供生育治疗选择，并将确定某些遗传异常 NOA的原因。 本建议书中描述的所有目标和任务都基于Jenkins 希尔实验室此外，商业化计划和NOA指南的成功建立在 由Inherent Biosciences开发的详细财务模型和市场启动计划-一家理想的公司 执行本研究的所有方面。在NIH SBIR快速通道拨款的支持下， NOA指南将为医生和患者提供前所未有的mTESE机会 成功和可能导致NOA的遗传异常。此外，不适合mTESE的患者 将避免不必要的侵入性手术和大量的自付费用。

NIH SBIR Fast-Track Application: Inherent Biosciences SUMMARY/ABSTRACT Title: Novel Epigenetic Test for the Treatment and Improvement of Longitudinal Health-Outcomes for Men with Severe Infertility 39.7 million men worldwide (1% of the male population) suffer the severest form of male infertility: Non-Obstructive Azoospermia (NOA). These men have no identifiable sperm in their semen, greatly limiting their chances of having children of their own. In addition to the heartbreak of infertility, these men have been found to have much higher risks for many long-term health conditions including cancers, metabolic diseases, and neuropsychiatric conditions. The lack of sperm is usually their earliest indication of potential chronic and somatic concerns. Men presenting with NOA, according to the American Society of Reproductive Medicine, should always be screened for genetic conditions (including Klinefelter’s Syndrome and Y-chromosome microdeletions) and be directed to further genetic counseling if any are discovered. There is essentially one path that can be taken for patients with NOA to retrieve sperm cells: testicular biopsy procedures. Microdissection testicular sperm extraction (mTESE) is the most common testicular biopsy procedure and is performed by cutting open the testicles and identifying areas in the seminiferous tubules with possible pockets of sperm production. Sperm then can be removed from the tubules and used for fertilization of an egg. mTESE is extremely invasive and expensive (~$12,000 out of pocket) and only has a 40-50% success rate of finding any sperm. To give these men the best options for conceiving and long term health management, the Jenkins and Hill Laboratories at Brigham Young University (BYU), in collaboration with Inherent Biosciences (Inherent), are developing a new, single comprehensive diagnostic test that 1) predicts the success of mTESE with extreme accuracy to guide treatment of sperm retrieval and subsequent conception, 2) more accurately identifies the subtypes of all Y-chromosome microdeletions (which is an important prognostic indicator), and 3) identifies Klinefelter’s Syndrome. Termed NOA-guideTM, this diagnostic test will be available for use by all NOA men (1% of the male population). NOA-guide will determine the presence (or absence) of sperm-derived cfDNA in a semen sample to determine if sperm retrieval from the testicle is a viable fertility treatment option for men diagnosed with NOA and will identify certain genetic abnormalities causative of NOA. All Aims and Tasks described in this proposal are based on solid preliminary data from both the Jenkins and Hill laboratories. Additionally, the plan for commercialization and NOA-guide success are founded in detailed financial models and market launch plans developed by Inherent Biosciences - a company ideally situated to execute all aspects of this study. With the support of this NIH SBIR Fast-Track grant, NOA-guide will provide physicians and patients with unprecedented insight into the chances of mTESE success and the genetic abnormalities that may be causing NOA. Also, patients not suitable for mTESE will avoid unnecessary invasive procedures and significant out-of-pocket expenses.