May 26, 1999

Melbourne research creates drugs to "turn off" the process that destroys tissue and bone in arthritis.


Melbourne scientists have made an international breakthrough in the
development of new drugs to fight auto-immune diseases such as
rheumatoid arthritis and lupus.

A team from the Austin Research Institute in Heidelberg and the
Biomolecular Research Institute in Parkville have created a series of
drugs to turn off the inflammatory process that causes tissue and
eventual bone destruction in rheumatoid arthritis and similar diseases.

The drugs are being tested in the laboratory and should be ready for
clinical trials in two to three years.

Professor Mark Hogarth, acting director of the Austin Research
Institute, said the discovery was the culmination of nine years' work.
"This approach will revolutionise the development of new drugs to treat
these chronic and debilitating diseases," he said.

"It is a paradigm shift ... It is also a platform technology that will
pave the way for the development of drugs to treat allergy and asthma."

The Fc receptor is part of a family of receptors and other receptors in
this group are involved in allergy and asthma.

Professor Hogarth and Dr Maree Powell of the Austin and Dr Peter Colman, Dr Tom Garrett and Ms Kelly Maxwell of the BRI have discovered and patented the structure of the Fc receptor that plays a crucial role in the inflammatory process.

The Fc receptor acts as a "lock", preventing the release of inflammatory cells unless they are needed to fight infection.  People with autoimmune diseases, however, have aberrant antibodies, which open the Fc receptor lock, unleashing continuous inflammatory destruction of tissue.

"By knowing the shape of this lock we are designing drugs specifically to 'plug up' the key hole of the lock to prevent it being activated," Professor Hogarth said.

The head of rheumatology at the Royal Melbourne Hospital, Professor lan Wicks, said the Austin-BRI discovery was internationally regarded as a breakthrough.  "Auto-immune diseases have been in the too-hard basket in the past," he said.

"This is important because it allows us to make specific drugs to block an important pathway in the inflammatory process and, by being more specific, hopefully, they will be more effective and with fewer side-effects.  "

Professor Wicks said while existing treatments for rheumatoid arthritis, including anti-inflammatories and disease-modifying anti-rheumatic drugs such as methotrexate or gold, were effective for many people, they could have serious side-effects and did not work for all patients.  "There is still a great need for new and better treatment strategies for these common and often debilitating diseases," he said.

The research has been published this month in the international science journal Nature Structural Biology.

Professor Hogarth said "rational drug designing", that is, finding the
structure of a molecule and then designing a drug to fit, had become
possible only in the past five years because of advances in gene
technology and robotics.

The approach was far more sophisticated than the traditional "grind and find" method of testing natural compounds in the hope they might be effective.

Rational drug design was used to develop Biota's anti-flu drug, Relenza.

Other recent advances in arthritis treatment included improved
anti-inflammatories that did not cause ulcers.  Last year the US Food
and Drug Administration approved a new class of arthritis drugs,
including leflunomide.

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