Infertility is one of the significant problems, which is currently affecting tens of millions of couples worldwide. In those tens of millions of couples, around half of cases having a male factor either as a sole or contributory cause. As of now, we know that the most important reason of male infertility is asthenozoospermia which means poor/dysfunctional sperm motility. As it is a main cause of male infertility but still there is no drug that men can currently take for it to improve the chances of conception.
Infertile couples who are trying for years to get pregnant naturally, has to rely on clinical treatments such as In vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). These both treatments are very much expensive, invasive and are not guaranteed to provide you satisfactory result.
While there is clearly an unmet need for alternative treatments for male sub fertility, so the time, efforts and resources required for drug discovery are currently exorbitant. The cellular, physical and functional properties of human spermatozoa present unique challenges to researchers and the lack of an appropriate platform to analyze potential treatments further complicates the issue. However, Scientists from the University of Dundee believe that they have taken the first steps towards developing drugs to treat infertile men.
What is HTS?
The Dundee team scientist have developed and validated a high throughput screening (HTS) method that may help to find novel agents that improve sperm function.HTS (high throughput screening) automates the experimentation process to allow researchers to quickly identify active compounds, antibodies, or genes relevant to their work. As of now, while a cure for male infertility remains some way off. The Dundee team researchers, led by Dr Sarah Martins da Silva, believe their method has removed many of the barriers towards developing drugs to treat the condition of inability of getting pregnant in men.
Dr Martins da Silva says that as infertility is developing day by day and male infertility is incredibly common but there is nothing we can currently prescribe in the vast majority of cases. The main problem is that we really don’t know the exact answer how to correct sperm dysfunction either. Other issue is that sperm are absolutely unique cells, designed to survive outside the body and hugely specialized to swim, find and fertilize an egg. They are small and have virtually no cytoplasm, and the cell signaling pathways can be unlike other cells. As a result, sperm are incredibly challenging to study. We believe we have now taken the first steps towards helping millions of couples worldwide.
As we all know that alterations in intracellular calcium are fundamental to sperm function which include swimming and fertilization, and that fluctuations in calcium are due, in large part, to a sperm-specific channel named CatSper (Cation channel of sperm). So, with the lack of knowledge of a known specific molecular or receptor target, compound library high-throughput screening (HTS) is an alternative approach that has developed in recent decades.
However, Dr Martins da Silva and her colleagues worked with the University’s Drug Discovery Unit (DDU) to create a high-throughput assay platform to monitor intracellular calcium responses in sperm as a surrogate for sperm motility. Dr Martins da Silva says that it enabled us to identify hit compounds, which we were able to test on sperm and saw improved functional motility. We noticed enhanced functional motility when we tested two of the compounds on patient samples, which are exciting and hugely relevant for patients, albeit this is still very early days. As sperm-specific channel named CatSper (Cation channel of sperm) is unique to sperm, identifying a therapeutic compound for it potentially avoids systemic side-effects and making these candidates very attractive both clinically and commercially. After conclusion that high-throughput screening (HTS) can robustly and efficiently identify novel compounds that increase intracellular calcium in human spermatozoa and improve function, the researchers propose to use it as a cornerstone to drive forward drug discovery for male sub-fertility. This news was published online by the Human Reproduction journal.