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

用于治疗和改善严重不育男性纵向健康结果的新型表观遗传学测试

• 批准号: 10760354
• 负责人: Kristin R Brogaard
• 金额: $ 26.97万
• 依托单位: INHERENT BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2024-02-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10760354
• 关键词: Affect; American; Area; Biological Assay; Biological Sciences; Biopsy; Cardiovascular Diseases; Child; Chronic; Collaborations; Conceptions; Couples; DNA; DNA analysis; Data; Development; Diagnosis; Diagnostic tests; Ejaculation; Epigenetic Process; Failure; Fertilization in Vitro; Funding; Genetic; Genetic Counseling; Genetic Diseases; Genetic Screening; Grant; Health; Infertility; Klinefelter' s Syndrome; Laboratories; Left; Link; Longevity; Male Infertility; Malignant Neoplasms; Marketing; Metabolic Diseases; Methods; Microdissection; Modeling; Molecular Abnormality; Outcome; Patients; Physicians; Population; Procedures; Production; Protocols documentation; Reproductive Health; Reproductive Medicine; Research; Retrieval; Sampling; Seminal; Seminal Plasma; Seminal fluid; Seminiferous tubule structure; Severities; Small Business Innovation Research Grant; Societies; Solid; Testing; Testis; Uninsured Medical Expense; United States National Institutes of Health; Universities; Unnecessary Procedures; Y chromosome microdeletions; bisulfite sequencing; cell free DNA; clinically actionable; commercialization; cost; genetic counselor; genetic testing; health management; high risk; improved; infertility treatment; innovation; insight; male; male health; men; microdeletion; neuropsychiatry; new technology; novel; poor health outcome; prognostic indicator; sperm cell; subfertility; success; zygote

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.

NIH SBIR快速轨道应用程序：固有的生物科学 摘要/摘要 标题：用于治疗和改善纵向健康状况的新型表观遗传测试 严重不育的男性 全球3970万男性（占男性人口的1％）遭受男性最严重的形式 不育：非刺激性的无植物植物（NOA）。这些男人的精液中没有可识别的精子， 极大地限制了他们有自己的孩子的机会。除了不育的伤心欲绝之外 人们发现，对于许多长期健康状况，包括癌症， 代谢疾病和神经精神病疾病。缺乏精子通常是他们最早的迹象 潜在的慢性和躯体问题。根据美国社会的说法 生殖医学应始终筛选遗传状况（包括Klinefelter的综合征 和Y-chromosoms微缺失），并指向进一步的遗传咨询。 基本上有一条可以让NOA患者检索精子细胞的路径：睾丸 活检程序。显微解剖测试精子提取（MTESE）是最常见的检测活检 步骤，并通过切开睾丸和识别半成分管中的区域而进行执行 精子生产的口袋。然后可以将精子从试管中取出并用于受精 鸡蛋。 MTESE极具侵入性且昂贵（从口袋里赚了约12,000美元），只有40-50％ 找到任何精子的成功率。 为了给这些男人构思和长期健康管理的最佳选择， Brigham Young University（BYU）的Jenkins和Hill Laboratories与固有的生物科学合作 （固有）正在开发一种新的，单一的全面诊断测试，1）预测MTESE的成功 具有极高的准确性，可以指导精子检索和后续概念，2）更准确 识别所有Y染色体微缺失的亚型（这是重要的预后指标），3） 确定KlineFelter的综合征。称为NOA-GUIDETM，此诊断测试将供所有人使用 NOA男子（占男性人口的1％）。 NOA指南将确定（或不存在） 精液样品中的精子衍生的cfDNA，以确定从睾丸中的精子检索是否可行 被诊断出患有NOA的男性的生育治疗选择，将确定某些遗传异常 NOA的原因。 本提案中描述的所有目的和任务均基于詹金斯的坚实初步数据 和希尔实验室。此外，在 固有生物科学制定的详细财务模型和市场发射计划 - 理想情况下 位于本研究的所有方面。在这项NIH SBIR快速通道赠款的支持下， NOA指定将为医生和患者提供对MTESE机会的前所未有的见解 成功和可能导致NOA的遗传异常。此外，不适合MTESE的患者 将避免不必要的入侵程序和大量自付费用。