RESEARCHERS AT NUI Galway have made what could be a significant breakthrough in the treatment of Huntington’s disease.
The researchers discovered an enzyme linked with genetic mutations in Huntington’s disease and by interfering with the enzyme’s activity, they were able to turn down its harmful effects in cells in the lab.
The findings, published last night in the open access journal PLoS Biology, do not represent a cure for the degenerative disease, according to researcher Prof Robert Lahue, but could point to new ways to control its progression.
In Huntington’s disease, cells in particular regions of the brain die away, resulting in uncontrolled movement, emotional disturbances and mental deterioration.
The culprit is an inherited mutation that includes too many repeats of the DNA ‘letters’ CAG in a particular gene.
In a person that carries the Huntington’s mutation, the stretch of CAG repeats can grow even longer when some ‘good guy’ proteins that normally protect DNA become fooled by the initial mutation and start expanding it by adding more CAGs, explains Prof Lahue from the Centre for Chromosome Research.
This expansion is thought to affect how quickly the person’s symptoms will progress.
Lahue and his colleagues carried out experiments in yeast and human brain cells growing in the lab to find out more about this expansion process.
Their study, funded by Science Foundation Ireland, found that specific histone deacetylase complex (HDAC) enzymes are involved in expanding CAG repeats.
And when they interfered with the action of a HDAC in human cells in the lab, they could dampen down the expansion. “We can see about 75 per cent fewer expansions,” says Lahue.
As it happens, a drug that can inhibit the HDAC is already in preclinical trials in the US for another aspect of Huntington’s disease, says Lahue.
He is hoping to work with them to find out if toning down the enzyme can have the beneficial side-effect of slowing CAG expansions in the brain itself.
“In theory if we could slow down those expansions then it would delay the disease,” says Prof Lahue. “So the next step is to see [pre-clinically] if these HDAC inhibitors can slow new expansions in the brain.
I would love to know the answer to that question, it is burning in my mind right now.