PMT drug? Not yet

“Discovery raises hopes of drug for PMT,” says the headline in The Daily Telegraph . The newspaper article reports that scientists studying the condition have “isolated a protein linked to the condition, raising hopes that a drug could be developed to block its effects”. The research “may also have benefits for epilepsy sufferers”, the newspaper says.

The study behind the story was conducted in a laboratory where researchers looked at the molecular structure of particular receptor molecules in cells. This research has very little to do with premenstrual tension (PMT), the only link made in the journal article is in the “background” section where the researchers discuss that previous studies have shown that these receptors may be more common in adolescent mice and in rats in heat. The newspaper has overstated the link between these findings and PMT. The micro-imaging techniques in this study will be of interest to the scientific community but they are a long way from providing any benefit to humans.

Where did the story come from?

Dr Nelson Barrera and colleagues from the Department of Pharmacology and the University of Cambridge (UK), the Centre for Neuroscience at the University of Alberta (Canada) and from Aston University in Birmingham (UK) carried out this research. The study was funded by grants from the Biotechnology and Biological Sciences Research Council and from the Canadian Institute of Health Research. It was published in the peer-reviewed medical journal: Molecular Pharmacology.

What kind of scientific study was this?

This was a laboratory study conducted in cells, not living organisms, where researchers were interested in understanding the structure of cell receptors. These molecules act as gateways for the cell and are responsible for allowing chemicals in and out. In nerve cells, one of the chemicals responsible for decreasing nerves’ electrochemical activity is an amino acid called GABA. It works by binding to a receptor, one of which – the GABA-A receptor – can be made up of a variety of subunits.

The researchers wanted to understand the structure of the different types of GABA-A receptors, particularly the type that have a unique structure containing a particular delta-subunit instead of the more common arrangement of alpha and beta-subunits. The purpose of their study was to find a method that could determine the arrangement of these subunits.

The researchers used genes from rats, that when put into human embryo kidney cells produced GABA-A receptors containing the most common subunits found in the receptor cells: alpha, beta and delta. Using a method of tagging the subunits, the researchers were able to separate out and purify the different types of receptors.

In addition, the researchers used a type of imaging called atomic force microscopy (a highly specialised type of microscopic imaging technique that can scan the surface of structures at very high resolution) to ‘photograph’ the different receptor structures. They used complex labelling and imaging procedures to determine exactly how the molecules arrange themselves to form the GABA-A receptors.

What were the results of the study?

The researchers were able to isolate the different types of subunits, the majority of which assembled into receptors in particular combinations. Some unassembled subunits were also detected. The receptors that contained the delta-subunit showed different characteristics to the more common receptors (containing beta-subunits), i.e. they didn’t show any evidence of a characteristic called positive cooperativity – where binding in one molecule makes binding in a second easier.

What interpretations did the researchers draw from these results?

The researchers conclude that their findings extend what previous research had suggested about the structure of receptors in nerve cells. The advance represented by their results is the method they have developed for determining exactly how the receptors are oriented (which way up they are) on the platform during imaging. This, they say, is a method applicable to other types of protein and allows them to “solve the structure of receptors containing three different subunits”.

What does the NHS Knowledge Service make of this study?

This well-conducted study was set up to establish a method to investigate the molecular structure of cell receptors. However, it did not examine the relationship of these receptors or any other factors to PMT or epilepsy and the newspapers have overstated the relevance of the findings to women who suffer from PMT.

As one of the lead researchers is quoted as saying in the Telegraph, "It's a long jump between rats and humans, but if we can make it, and a similar thing occurs in humans before menstruation, changes in the level of this receptor could contribute to PMT." The question for people interpreting the results of this study is, ‘Can we make that jump?’ Only further studies will reveal what relevance this finding has for human females who suffer from PMT.

Sir Muir Gray adds...

From the cell to the human is a big jump.