Genetic Research: Moving Towards a Root Cause

August 7, 2017

Genetic investigations continue to make news in the world of migraine research.  As you may recall, last year (2016) our newsletter reported a number of major genetic advances.  In probably one of the best known to date, originally published in Nature Genetics, an international group of researchers isolated 38 genetic variants implicated in migraine, 28 of them previously unknown. This research remains significant for a number of reasons, not the least of which is finding an answer to one of the central questions of the etiology of migraine disease - Is migraine disease vascular or neurological in nature? This study revealed the majority of the genes found in migraine regulate the vascular system. This was a major step forward in the understanding of migraine disease and ultimately the treatment of it.

Now fast forward to the present. Again, genetics finds itself in the news in a big way. In the July 27, 2017 issue of the Journal Cell, genome-wide (the complete set of genes or genetic material present in a cell or organism) association studies have connected a common genetic variant in five different vascular diseases. These are coronary artery disease, migraine headache, cervical artery dissection, fibromuscular dysplasia, and hypertension. It is unclear at this point exactly how the presence of genetic variation within the same population affects the risk for so many diseases. In this study researchers demonstrate how this DNA variant enhances the activity of a particular gene which is known to promote vasoconstriction and hardening of the arteries.

Put differently, "the main value of our research is the pinpointing of the importance of endothelin-1 (ET-1) and blood vessel constriction to multiple vascular diseases," says senior author Sekar Kathiresan. Past studies have shown that ET-1 is the strongest, most robust vasoconstrictor in humans, and it stimulates the growth of plaques inside the arteries. "We also show how to identify a core gene for multiple diseases through genome editing in cells."Genome editing is a method of making precise changes to the DNA of a cell. An enzyme cuts the DNA at a specific sequence, and when this is repaired by the cell a change or 'edit' is made to the sequence. All of this can have powerful, positive, clinical implications.

Genetic related vascular and/or migraine research has seen an explosion in the past few years, along with the attendant technology. In general, there have been enormous strides made on many of the differing migraine "fronts".  Genetics is in the spotlight this month, but this enthusiasm should be tempered by the reality that a genetic cure may actually be years away. Other areas of investigation, such as CGRP antibodies, or neuromodulation hold the possibility of much shorter term solutions. This is not to say that all of these possible remedies may not have a common denominator, or root cause.It is highly likely they do and that root cause is genetic.