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.

Grant Number: 5R44HD112264-03
NIH Institute/Center: NIH
Principal Investigator: Kristin Brogaard