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

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.