An international effort to pinpoint the genetic causes of epilepsy could help pave the way for better treatment of the condition, writes Dick Ahlstrom.
Irish scientists are involved in an international collaboration to identify the genetic causes of epilepsy. The study has delivered important new findings that bring closer the possibility of personalised treatments for the condition.
"What we were trying to do is find genetic factors that predispose a person to epilepsy," explains Dr Gianpiero Cavalleri, a research lecturer at the Royal College of Surgeons in Ireland.
The large-scale international study involved more than 2,700 epilepsy patients and four centres in the "Epigen" consortium, a collaboration that brings together the RCSI and teams at University College London, Duke University in the US and Erasme Hospital in Brussels.
Details of the Epigen study were published last month in the journal Lancet Neurology.
The research approach taken by the consortium was made possible both by the human genome project and more importantly the creation in 2002 of the HapMap Project, explains Dr Cavalleri.
This is an international effort to help researchers find genes associated with human disease and how they respond to drugs.
HapMap was finished just last year but catalogues the genetic variation that exists between individuals, he says. It is based on looking for "snps" or single nucleotide polymorphisms, usually called "snips".
Early detective work to track down the genetic causes of disease enjoyed early successes where the illness was linked to a single gene. Researchers soon found, however, that most diseases involved a complex mix of gene activity. "We had to develop new methods of analysis to tackle that problem," says Cavalleri.
Snips were the answer. "A snip is a position on the genome at which two people differ," he explains. "They aren't mutations or disease causing; most are neutral but some affect how we are different from one another."
One outcome can be susceptibility to a particular disease, hence the interest of the Epigen consortium in snips that might be linked to epilepsy.
The group used a technique to scan through the huge numbers of snips involved in the 2,700 patients.
It meant they didn't have to look at every snip, just specific ones called "tags", snips that were correlated with others so only one had to be identified to predict the presence of others.
The approach was "all quite new", says Dr Cavalleri but it provided enough shorthand to speed up the analysis. "We used that method to look at 279 candidate genes for 4,500 tags."
The method is developing over time, he adds, with more power coming into the analysis.
It means that scientists are getting closer to being able to look at 500,000 snips for common variations in the genome.
"You are truly looking at the genetic contribution to human disease."
He stresses that diseases are usually triggered by genetic and environmental causes, but being able to separate out the genetic component would be a considerable advance.
"It is going to tell you about new biological pathways that lead to the development of disease," he believes.
Importantly, it will also open up the possibility of customised treatments and personalised prescribing. The presence of certain snips will indicate whether a particular drug will prove effective or cause too many side effects. Understanding the patient's genetic mix will help deliver personalised treatments.
Dr Cavalleri also highlighted the collaborative approach involved in the Epigen consortium, something that is vital when looking at the human genome and its three billion base pairs.
"Prior to Epigen there wasn't much collaboration between groups." This meant that teams often conducted duplicate research.
Now the work can be shared and everyone knows what the other groups are doing. "It really speeds up the discovery process," says Dr Cavalleri.