Getting Men Over the Infertility Hump
You’ve heard of gene therapy right? What ever happened to it? Born back in the 1990’s, the same decade that Viagra was introduced to the world, gene therapy has not fared nearly as well as the little blue pill.
Why not? First of all, gene therapy, in which DNA is put into cells to treat disease, is not your average “drug.” Putting working genes back into patients with faulty ones requires that we know the precisely the genes at fault. Unfortunately, most diseases are polygenetic or have no known genetic causes, which makes it difficult to treat them in this way. Then, you have to get the gene into the right place in the genome and hope like hell that it does more good than harm (i.e. tumors). Not only that, gene therapy effects may be short-lived, and can be very, very expensive, reportedly costing up to $1.6 million per patient. But, alas, these issues are either manageable or knowable; gene therapy is here to stay.
Gene Therapy for Sperm?
Ok, I know we’re at the table a little late, but we just published a gene therapy trial of our own. The goal was to see if we might be able to cure genetic infertility. One common cause of azoospermia (no sperm in the ejaculate) is deletions on the Y chromosome. Conveniently, the gene regions at risk are called a, b and c. Men with these gene deletions can be missing not only sperm, but also the sperm precursor cells called “early germ cells.” In other words, the entire early gem-cell-to-sperm sequence is absent. This is pretty devastating, since techniques like FNA mapping are doomed to fail in such cases. In the world of medicine, genetics get a whole lot of respect.
Gene Therapy to the Rescue
In our germ line, gene therapy study, here is the recipe we followed.
- We took a skin biopsy from an azoospermic patient with a gene deletion in the “a” region of the Y chromosome.
- We turned those skin cells into stem cells in a dish, which is actually routinely done nowadays.
- We replaced one of the missing genes (DDX3Y) back into the Y chromosome of the stem cells.
- We put the “treated” human stem cells into mouse testicles, which kinda mimics it’s natural “home,” the human testicle, and let them grow.
- We watched what happened. Lo and behold, banks of genes turned on in those little skin-derived stem cells that looked remarkably similar to early germ cells heading down the path toward sperm. They actually began to remodel and take the look and character of actual sperm precursor cells!
In other words, gene therapy partially “rescued” the genetic program that stem cells normally use to become sperm, a process that is absent in men with certain Y chromosome deletions. Not only that, it appears that this little Y chromosome gene is an early and important regulator of sperm production. Finally, it portends a future in which gene therapy may be used to overcome genetic infertility by helping the reproductive system get “over the hump” posed by missing fertility genes during fetal life, and thereby allow for free flowing sperm production later in life.
One small step for man, but what a conceptual leap for his future on this good earth!