[ASC-media] New research could PAC punch against arthritis

Sarah Brooker sarah.brooker at gmail.com
Tue Aug 15 13:31:34 CEST 2006

Embargo 10am Wednesday 16 August

RESEARCHERS in Sydney have discovered that an enzyme only found in immune
cells plays a key role in promoting rheumatoid arthritis. The work raises
the possibility of new and better treatments for the painful and
debilitating condition, which affects about one in a thousand Australians of
all ages.

Dr Kate Jeffrey and her colleagues at the Garvan Institute of Medical
Research found that the enzyme known as PAC-1 is responsible for directing
the activities of the immune cells which cause rheumatoid arthritis. Their
work was published recently in the respected scientific journal, Nature

"PAC-1 helps immune cells to respond to the body's signals for help against
infection in three critical ways," Jeffrey says. 

"It assists the immune cells to survive, to migrate to where the emergency
is, and to release potent inflammatory compounds at the site. And PAC-1 is
only one member of a whole family of enzymes that can instruct immune cells
in this way. So our studies may lead to better therapies for many other
autoimmune and inflammatory diseases."

Rheumatoid arthritis differs from the more common degenerative arthritis of
the elderly, osteoarthritis. It is caused by over-protective immune cells
which mistakenly attack the body's own cartilage, the material which
lubricates the movement of joints. As the cartilage deteriorates, the
movement of bone against bone becomes very painful. 

"Despite mounting knowledge of how and why the disease develops, effective
treatments are limited," says Jeffrey. "At present they focus on damping
down the activity of the cartilage-damaging compounds the immune cells
release, using drugs such as TNF-inhibitors, the controversial COX-2
inhibitors like VIOXX or broad-spectrum immunosuppressants. Many patients
either do not respond to these drugs or develop severe side effects."

Jeffrey and her colleagues found the enzyme by scanning all of the genes
present in human immune cells. They discovered that the gene for PAC-1 was
only ever "switched on" in immune cells. 

It produces high amounts of the enzyme when the immune cells are triggered
into action by encountering a threat to the body, such as a bacterium. But
the enzyme is also produced in abundance where overactive immune cells
accumulate in human rheumatoid joint tissue. 

Animals lacking PAC-1-where the gene is "knocked-out" in mice, for
instance-fail to show any symptoms of rheumatoid arthritis such as swollen
joints, Jeffrey says. "Inhibition of PAC-1 is therefore a real potential
strategy for controlling the overactive immune cells responsible for
rheumatoid arthritis without affecting other systems in the body. This is a
completely different approach to current therapies."

The research team is now engaged in collaborative research aimed at
developing and trialling a drug which can inhibit PAC-1.

Kate Jeffrey is one of 16 young scientists presenting their research to the
public for the first time thanks to Fresh Science, a national program
sponsored by the Federal and Victorian Governments. One of the Fresh
Scientists will win a trip to the UK courtesy of British Council Australia
to present his or her work to the Royal Institution.

For further information or an interview contact: Kate Jeffrey on (02) 9295
8423 or 0402 908 905 or  k.jeffrey at garvan.org.au

Garvan Medical Research Institute: Branwen Morgan, Communications Manager on
(02) 9295 8135 or 0434 071 326

Media contact for Fresh Science: Joanna Gajewski on 0429 388 822 or
jo at freshscience.org 

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