Australian researchers studying Huntington's disease in human embryonic stem cells say that signs of the disease can be seen in cells just a few days old.
The researchers, from Macquarie University's Australian Proteome Analysis Facility (APAF) and IVF Sydney, say they are the first in the world to study Huntington's disease in human embryonic stem cells.
'Human embryonic stem cells provide us with a very good model for doing drug toxicology and efficacy testing.' — Dr. Leon McQuade
Dr. Leon McQuade, the senior scientific officer at APAF, presented the research Wednesday at the Human Proteomics Organization congress in Sydney.
Huntington's disease is a fatal genetic brain disorder affecting about one in every 10,000 Canadians, according to the Huntington Society of Canada. Symptoms are usually first seen in middle age and become progressively worse.
Until now, studies into how the disease develops could only be done in mouse models, which do not always accurately reflect the disease in humans, or in brain cells of patients after they have died.
Changes in young cells
Recently, researchers have examined human embryonic stem cells taken from five- to seven-day-old embryos that were known to have Huntington's and had been donated by couples undergoing genetic testing before IVF.
The researchers looked at how the mutation affects cells by comparing protein production in Huntington's and normal cells. The strongest difference was seen in proteins associated with mitochondria, the batteries of cells.
There has already been evidence of mitochondria being affected in Huntington's, but this evidence has come from much later stages of the disease — two-week-old mice and adult people.
McQuade says being able to see these changes in such young cells could change the way researchers think about Huntington's disease.
"This is the first study, using embryonic cells, where we're actually seeing mitochondrial dysfunction even before differentiation into neurons," he says.
He says the task now is to understand how the mitochondria are disrupted, with a view to one day developing drugs.
'Horrible and fatal disease'
"Human embryonic stem cells provide us with a very good model for doing drug toxicology and efficacy testing — it's a model that we really haven't had before."
Professor Anthony Hannan, head of the Neural Plasticity Laboratory at the Howard Florey Institute in Melbourne, says it's exciting to see new research into Huntington's disease "because it's such a horrible and fatal disease".
Hannan says the findings reflect those found in other studies, validating the use of human embryonic stem cells in this way. But the research must be verified in more human embryonic stem cells from separate embryos, he says.
To confirm that the protein changes are due to Huntington's and not simply genetic changes between the cells of different embryos, McQuade and his collaborators will be validating the results in the coming months using four Huntington's cell lines that are now available.
Hannan says induced pluripotent stem cells could also be created from the skin cells of live Huntington's patients. This would mean that changes in the cells could be compared with their specific symptoms.