Although female oral contraceptives have proven effective for family planning for the past 40 years, there is currently no male oral contraceptive on the market.
However, University of Iowa researchers report a newly discovered genetic abnormality that appears to prevent some men from fathering children. This genetic abnormality may be the key for researchers to develop a male contraceptive.
Michael Hildebrand, PhD, postdoctoral research scholar, and co-lead of the study, with University of Iowa Health Care, talks about the genetic abnormality that might lead to an oral contraceptive for men:
What was the initial intent of the study that lead to the discovery of this abnormal gene?
In our laboratory we study a variety of genetic diseases, including hearing loss and kidney diseases, and also infertility. We identified the Catsper1 mutations involved with infertility in two Iranian families in which some males in those families had infertility. We were able to identify the mutation and gene responsible for infertility by comparing individuals with and without infertility in those two families. We were able to look closely at their DNA and we could identify the particular variation that was responsible for the infertility in these males.
How did a study focusing on identifying genetic causes of deafness come across two families where male infertility appeared to be inherited?
As part of those studies, we look at a large number of different families and many of these families have hearing losses and kidney diseases, but they also have other diseases that are inherited along with the hearing loss and with the kidney disease. In the process of looking at these families, we came across two families where the males were infertile. We then went on to look at identifying that particular gene involved.
What steps were taken to find this genetic disorder in these two family lines?
Basically the two steps were to take individuals that had infertility and individuals that had normal fertility and compare the DNA between those sets of individuals within these two families and then identify a variation which was only seen in those individuals that had the infertility.
By identifying the gene, can the families with inherited male infertility be treated?
It may be possible in the future to actually replace defective Catsper1 gene or protein in these patients with this particular type of infertility. However, this cannot be done at present. This type of gene replacement has been shown to be effective in animal models, but has not yet been shown to be safe to attempt in humans. If we were able to put the normal gene back into the sperm in the future, it should be possible to restore normal movement of the sperm and therefore allow fertilization to take place.
How will identifying a gene that causes infertility in men help in the development of an oral contraceptive for men?
We may be able to use a drug that is known to target this particular Catsper1 protein, and which could potentially disrupt its function. For example, we could use a drug that binds the protein and interferes with its normal function, and this would affect the ability of the sperm to swim in and then prevent fertilization of an egg. If we were able to identify such a drug that could really target this protein—and if we were ever sure that it was safe in animal models—we could then move on to clinical trials in humans.
What are the next steps in the process in developing this birth control medication for men?
The next step is to identify a drug that’s both safe and effective and that specifically targets this Catsper1 protein. If we’re able to do that then we need to make sure that when we use it in animal models that it’s safe, and then we could attempt to use it in human individuals.
How many years before a medication will be pproved for men interested in an oral contraception?
These type of animal studies and then clinical trials are normally long-term trials and so we’re looking at probably somewhere in the range of five years before we would be able to trial such a drug in humans. |
