Scientists are preparing to test a potential therapy for Huntington’s disease in sheep that have been genetically modified to carry the mutation that causes the disease.
Researchers at the Auckland University Centre for Brain Research are at the heart of the Huntington’s sheep project. They developed the first large-animal model of a neurological disorder, although the flock is at a research institute in South Australia and has been made available for international studies.
The disease is caused by mutations in one copy of the “huntingtin” gene inherited from one parent. The faulty gene produces an abnormal protein with an expanded repeat sequence, like a longer-than-usual bike chain. It builds up brain cells and kills them, causing abnormal movements, loss of co-ordination and personality changes.
The experiment, led by US scientists, will introduce so-called “interference RNA” into some of the Huntington’s sheep’s brains. The aim is to disrupt the process by which the gene’s DNA is “read” or transcribed into RNA and the RNA is translated into protein of a particular shape.
The interference RNA comes in a safe virus that is injected through a hole made in the skull – similar to the method used in a trial gene treatment of humans with Parkinson’s disease.
It is hoped the RNA will bind to the faulty huntingtin RNA and prevent its being read into faulty protein. In this way it would halt the brain cell damage caused by the protein. This is a potential therapy for people with the faulty gene, but it would not prevent the on-average 50 per cent chance of a child inheriting the mutation from an affected parent.
“We’re putting in something that will interfere with the gene and in effect switch it off,” said Professor Richard Faull, a leader of the overall Huntington’s sheep project and director of the Centre for Brain Research.
He expected it would take five years to produce results from the trial, which would start this year or early next year.
Sheep project co-leader Professor Russell Snell said: “One of the challenges of this approach is that we know we need the normal version of the protein which is produced in all of us. So while knocking down the bad version of it, we want to retain the good version. And so another question in this experiment is, can we target just the version carrying the mutation.”
The Centre for Brain Research says it is Professor Snell’s skills that enabled the entire human gene for Huntington’s disease to be incorporated into sheep embryos.
Professor Faull said some of the sheep were now approaching 6 years old and had developed some of the very early Huntington’s changes in the brain, although they had no outward symptoms and were not suffering.