A TCD researcher is digging into our ancestral gene pool, the "Celtic code", that may guide the way towards more effective treatments for degenerative brain diseases, reports HELEN GALLAGHER
The focus is on the seriously debilitating motor neurone disease (MND), explains Prof Orla Hardiman, consultant neurologist at Beaumont hospital and clinical professor of neurology at Trinity College Dublin.
This is the disease that has left world-renowned British cosmologist and author, Prof Stephen Hawking in a wheelchair and unable to speak.
“The multi-disciplinary research team has been clinically investigating motor neurone disease, a neurodegenerative disease which causes a gradual degradation and death of motor neurones,” she explains. “One in every 400 in Ireland is at risk of developing Motor Neurone Disease during their life-time.
Her groundbreaking research recently won Hardiman the Sheila Essey Award for significant contribution to research into the cause and prevention of MND.
A combination of global funding and expertise has come together in this extensive research project. Funding from the Health Research Board, along with the Irish and the American Motor Neurone Associations, has made this research possible, explains Hardiman.
Ireland has a very good population for the study of neurological disease, she says. “There has been very little immigration until recently, so genetically the population is relatively homogenous, with good access to healthcare, so it is possible to look at diseases at a detailed level.
“I initially set up the MND register capturing all sufferers in Ireland in 1994. We are able to follow every Irish patient from the time of diagnosis, so this is a very powerful tool to research information.”
Examining the register shows some surprising disease patterns across the country. “We have been able to track the disease over 15 years, and have established that there has been a movement westwards in the increase in frequency of MND in Ireland.”
The research has examined environmental influences across Europe, she explains. “Looking into European genetic and environmental susceptibility, we identified a number of genes in the Irish population, and were able to replicate these in the Scottish population. This was very reassuring as the genetic make up of the Irish and Scottish is very similar.”
A breakthrough for the Irish team came with the isolation of a gene directly associated with MND. “We discovered that mutations in the ANG [angiogenin] gene lead to motor neurone death.”
Research in Trinity College is homing in on parts of the genome related to MND, explains Hardiman. They are using clipped sections of the genetic code called “SNiPs” . “These clips of genetic code have allowed a genome wide association study, and to compare the variation across the Irish and Dutch populations. Differences in the variants could be attributed to the older, and more isolated genetic ancestry of the Irish,” she said.
“The ancestral link in genes between Ireland, the Basque Country, Wales and Scotland on the RTÉ television program Blood of the Irish is evident,” says Hardiman. “The further west in Ireland we go the more ‘pure’ the ancestral genetic population, and the higher the frequency of MND.”
Data from studies abroad are also informing her work. “In Cuba we found the frequency [of MND] in this genetically mixed population was much less than the Spanish, or white-skinned category.” This in turn supports the view that causes are more likely genetic rather than environmental.
“Cuban data also suggested this may be the case for Parkinson’s and Alzheimer’s disease, which is extremely exciting as it has opened up a whole new area of research into mixing genes to confer protection against these diseases too.”
Family linkage is also being explored.
“Families of MND sufferers are four times more likely to have had dementia, Parkinson’s or Alzheimer’s disease. We want to establish if susceptible genes manifest to different degrees in some families,” says Hardiman.
“This is a really exciting area, and a really exciting time.”