The Huntington's Scene In
New Zealand
Site Maintained by
Graham Taylor
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| Articles taken from the MARCH
2005 Huntington's News. The Quarterly Newsletter of the Huntington's
Disease Associations of New Zealand |
STOPPING
THE BRAIN DRAIN
What if the injured brain could repair itself? JOANNA WANE meets a young scientist whose research aims to
stimulate stern cells to go on fix-it missions.In the universe of the human
body, the brain is largely uncharted space which has only in recent years begun to surrender its deepest secrets to scientific
inquiry.A highly complex command centre controlling memory, movement and even our moods,
it was always believed to have one fatal flaw: that it lacked the capacity for self
repair.
This
theory was finally debunked in 1999. Researchers in California analysing brain tissue from
cancer patients who had been rejected with a dye that labels dividing cells, stumbled
across something unexpected: not only did the adult brains contain stem cells, those
cellular building blocks thought to exist only in the brains of newborn babies; they were
able to divide and create new brain cells.
Then
University of Auckland pharmacologist Dr Bronwen Connor dropped a bombshell of her own. In
research funded by the New Zealand Neurological Foundation, she discovered that, in adults
with brain disease, stem cells responded to a distress call from the area under attack by
sending out reinforcements on a rescue mission to replace brain cells that had died.
That,
says Connor, was a revolutionary concept. “The whole regenerative side of the brain
was thought to be non-existent. But this opened up a whole new set of ideas about the
potential treatment of brain disease and injury.”
In
brain tissue bequeathed by patients suffering from the degenerative neurological disorder
Huntington’s disease, a team led by Connor and Professor Richard Faull (of the
University’s Anatomy Department) found more stem cells than normal in the brains of
Huntington’s patients. New brain cells had started to form.
Next,
she tracked the development of stem cells in brain tissue from rats with Huntington’s
lesions. Again, the cells began to replicate. Then they went on the move, spreading like
an invading army into the damage zone. The brain it seemed, was trying fight back.
Connor,
who spent three years in Chicago doing her post-doctoral fellowship, says it was
particularly satisfying to share such a significant breakthrough with colleagues in the
United States. “It absolutely polarized views,” she says. “Some thought it
was incredibly exciting; others were a bit skeptical and said, ‘Show us more’.
When people react like that, you know you’re onto something.
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“IT ABSOLUTELY POLARISED VIEWS
SOME THOUGHT IT WAS INCREDIBLY EXCITING;
OTHERS WERE A BIT SCEPTICAL AND SAID, ‘SHOW US MORE’. WHEN PEOPLE REACT LIKE
THAT YOU KNOW YOU’RE ONTO SOMETHING.”
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In September, she
launched a $700,000 project, funded by the Health Research Council, to prove the sceptics
wrong. Connor, 31, a senior lecturer in the Faculty of
Medical and Health Sciences, is widely respected as one of the University’s most
talented young scientists. A keen athlete who represented New Zealand in rowing, she
initially planned to do sports physiology before being drawn into pharmacology, then
deciding to specialise in neurological research.
‘The
brain is a fascinating organ that does so many different things,” she says. “We
keep finding that it has more and more potential. And because it’s associated with
our individuality and our personality, it’s always thought of as something special.
The only other organ that comes close is the heart”.
The
project that Connor is heading will focus on Huntington’s disease, an inherited
disorder that affects about one in 15,000 New Zealanders. Currently untreatable, it
short-circuits the part of the brain that controls movement, causing a slow, insidious
deterioration of motor function over a period of 10 to 15 years.
The
reason for focusing on Huntington’s is that the part of the brain destroyed by the
disease sits right alongside the strip where stem cells cluster, so new migrating brain
cells don’t have to travel far to do their work
Connor
believes the brain already goes into fix-it mode when damaged by trauma or disease –
but it’s too little, too late. The focus of the research is to enhance that natural
process, by stimulating the formation of new brain cells and luring them to where they are
needed to replace the functions being lost.
If successful, the same technique could be
applied to the treatment of brain injuries and a whole range of neurological disorders,
including stroke, epilepsy, and Alzheimer’s and Parkinson’s diseases.
Two
experiments, both using gene transfer techniques, will run in parallel during the
three-year project. In the first, stem cells in a cultured brain tissue from rats with
Huntington’s lesions will be “tagged” with a viral vector. The virus itself
is harmless – its disease-causing elements are carefully removed before insertion
– but it infects dividing cells and makes them glow under a fluorescent light.
What happens next tests the belief that specific
proteins in the brain play a role in stimulating
stem cell renewal. A dot of these proteins will be dropped on to the diseased tissue and
also onto a sample of healthy tissue. Both will then be videotaped, using time-lapse
imaging, every three hours to track the migration of the labeled cells in response to both
the delivered protein and to cell loss in the diseased tissue.
In the second experiment, a gene carrying the
proteins’ DNA will be injected directly into the striatum of rats with Huntington’s.
The
striatum is the part of the brain that controls movement and is affected by the disease.
This time, instead of infecting only dividing cells, the virus on the gene will distribute
proteins indiscriminately, in an attempt to encourage the creation of new brain cells and
attract them to the key site of cell destruction
Equally
important is finding out whether this fresh supply is of brain cells is the right type to
start taking over brain functions that have been impaired. One way of testing this will be
to analyse the rats’ motor skills, to see if there is any reversal or slowing in the
degenerative effects of the disease.
The
migrating brain cells make relatively speedy progress, says Connor. In rats, they’ve
been tracked from the middle of the brain to the olfactory bulb in the nose in less than
seven days. Inching along like microscopic caterpillars on their heroic journey, they
stretch out feathery-looking feelers, constantly searching for a new connection.
Connor’s
own career pathway has been all about making the right connections, too. Her research team
co-leader, Professor Richard Faull, was one of her PhD supervisors and is the director of
the New Zealand Neurological Foundation Brain Bank which stores tissue bequeathed for
medical use – an invaluable resource that Connor has drawn on for her ground-breaking
research.
In
Chicago, Connor spent three years at Northwestern University at a time when the
controversial field of gene therapy first erupted on the scene – becoming trained in
techniques which are at the heart of her brain-repair project today.
From
there, she returned home in 2000 to set up her own laboratory where she now leads a team
of 10.
Still
in its infancy, research on brain repair is a fast-moving field internationally and the
potential for limiting or reversing critical damage is enormous.
Although
not directly involved in clinical trials, Connor says that she never loses sight of the
human cost of neurological disorders. Her grandmother suffered from Alzheimer’s and
she has regular contact with families affected by Huntington’s disease.
“They
remind you exactly what you’re doing and why,” she says.
Acknowledgement:
This article was
written by Joanna Wane
and appeared in
Ingenio– Magazine of the
University of Auckland – Spring 2004