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

NIH SBIR快速通道应用：固有的生物科学 摘要/摘要 标题：治疗和改善纵向健康的新表观遗传学测试-结果 严重不孕症男性 全世界有3970万男性(占男性人口的1%)患有最严重的男性疾病 不孕症：非梗阻性无精子症。这些人的精液中没有可识别的精子， 极大地限制了他们拥有自己孩子的机会。除了不孕不育令人心碎之外，这些 研究发现，男性患包括癌症在内的许多长期健康疾病的风险要高得多。 代谢性疾病和神经精神疾病。缺乏精子通常是他们最早的症状 潜在的慢性和躯体问题。根据美国医学会的数据，男性与NOA一起出席 生殖医学，应始终筛查遗传疾病(包括克氏综合征) 和Y染色体微缺失)，如果发现任何遗传咨询，则将其引导至进一步的遗传咨询。 基本上，NOA患者可以选择一种途径来获取精子细胞：睾丸 活组织检查程序。显微分离睾丸精子提取是最常见的睾丸活检方法。 手术是通过切开睾丸并识别生精小管中的区域 可能产生精子的地方。然后，精子可以从小管中取出并用于受精 一个鸡蛋。MTESE侵入性极强且价格昂贵(约12,000美元自掏腰包)，而且只有40%-50% 找到任何精子的成功率。 为了给这些男性提供怀孕和长期健康管理的最佳选择， 杨百翰大学(BYU)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，该测试可以预测mTESE的成功 以极高的精确度指导取精治疗和后续受孕，2)更精准 确定所有Y染色体微缺失的亚型(这是一个重要的预后指标)，以及3) 确认为克莱菲尔特综合征。这项名为Noa-GuideTM的诊断测试将可供所有人使用 无男性(占男性人口的1%)。NOA-GUIDE将决定是否存在 精液样本中精子来源的cfDNA以确定从睾丸取精是否可行 诊断为NOA并将识别某些基因异常的男性的生育治疗选择 NOA的因果关系。 这份提案中描述的所有目标和任务都基于来自詹金斯夫妇的可靠的初步数据 和希尔实验室。此外，商业化和Noa-Guide成功的计划建立在 由Inherent Biosciences开发的详细财务模型和市场推出计划-理想情况下是一家公司 定位于执行这项研究的所有方面。在NIH SBIR快速通道赠款的支持下， NOA-GUIDE将为医生和患者提供对mTESE机会的前所未有的洞察 成功和可能导致NOA的基因异常。此外，患者不适合进行mTESE 将避免不必要的侵入性程序和巨额自付费用。

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.