The little mouse who wouldn't say die

http://www.cosmosmagazine.com/node/471

The little mouse who wouldn't say die
26 July 2006
by Carmelo Amalfi
Cosmos Online

When a little laboratory mouse refused to die of mesothelioma, an Australian
biotech company suspected they might be on to something big.
Laboratory rats rarely retire. For most 'guinea pigs' of science, death by
disease or drug overdose is the only way out of the experiments.

But what happens when one of the subjects survives all the tests? And not
just once, but twice.

For starters, share prices jump and so do the hopes of thousands of
asbestos-related mesothelioma sufferers around the world.

Meet Mouse Number Five, the humble little lab mouse that survived one of the
world's nastiest and incurable industrial diseases.

Known as M5 to his lab mates, the 'miracle' mouse is still living it up on
free cheese in quarantine - a living symbol of what can be achieved when
biotechnology and business mix, according to Solbec Pharmaceuticals general
manager David Sparling.

M5 made the front page last year when the Perth-based company announced that
the infected lab mouse recovered from mesotheliolma after he was
administered drugs made from compounds extracted from the fruit of devil's
apple, a noxious weed introduced from Africa to Queensland in 1801.

The plant-based drug they developed, coramsine, 'cured' M5. He also survived
after he was re-infected with the normally deadly disease - suggesting that
coramsine gave him lasting immunity by boosting or 'priming' the immune
system to respond to tumour attacks.

Sparling said the same result had been observed in limited trials of
terminally ill patients in WA, whose tumours either shrunk or disappeared:
"M5 represents a significant step in our mesothelioma research. It did not
mean it would work in humans, but it did not mean it wouldn't."

Mesothelioma is a malignant growth in the cells that line a patient's body
cavities including the chest, abdominal region or tissues surrounding the
heart. It is typically associated with exposure to fine fibres of asbestos
used for decades in Australia in the manufacture of building products now at
the centre of the nation's biggest industrial health scandal.

Up to 45,000 people are expected to die from mesothelioma over the next 15
to 20 years, with more than 2500 Australians a year diagnosed with
untreatable asbestos-related diseases such as mesothelioma.

One of five mice infected with the disease as part of Solbec's phase one
trials to prove coramsine's safety and level of toxicity, M5 has now moved
on to greener pastures - one of the lucky few lab rats set to die of natural
causes.

Two other mice pulled through the phase one toxicity trials, but died of an
overdose. And another two were put down after their tumours shrank, then
returned.

Sparling said the focus now was repeating the M5 test results in national
clinical trials over the next 12 to 24 months. Not on mesothelioma, but two
other killers of Australians - malignant melanoma and renal cell carcinoma.

He said the trials will take the company's drug therapy treatment from phase
one to phase two trials, proving efficacy in people. They will involve up to
60 patients with malignant melanoma and up to 60 patients with renal cell
carcinoma from hospitals in every state and territory.

From there, if successful, Solbec moves to phase three - taking the drug to
the marketplace. Originally incorporated as a mining company (Britannia
Gold), Solbec was re-listed as a biotechnology company in 2001.

Sparling said it was best to have phase two results before little biotechs
such as themselves establish partnerships with much bigger companies with
the resources and marketing channels to take it through to consumers
worldwide.

Solbec in Perth employed 16 people specialising in the development and
commercialisation of therapies for life threatening and debilitating
diseases and disorders, including biopharmaceutical compounds for the
treatment of cancers such as melanoma, renal cell carcinoma and malignant
mesothelioma. Devil's apple is one of those "therapies".

Known in scientific circles as Solanum linnaeanum, the Devil's apple's
active compound, coramsine, consists of two main compounds, the
glycoalkaloids solasonine and solamargine, which act by binding to a
receptor on the cancer cell and rupturing the cell wall, causing the cell to
die.

Solbec has located a receptor it believes is common to most cancer cells.
Studies at the University of Western Australia have shown activity against
ovarian cancer, renal cancer, melanoma, mesothelioma, colorectal and colon
cancer, gastric cancer, bladder cancer, various skin cancers and prostate
cancer.

The applications of devil's apple in combating cancer was tested and
patented in the early 1980s by Bill Cham, who was then a medical researcher
at the University of Queensland.

Cham, who developed a cream made from the devil's apple flower, followed up
anecdotal evidence from livestock owners that the growth of skin cancers and
lesions had slowed down or cleared up in horses and cattle that ate the
weed.

Farmers also were known to rub the sap of the fruit to the back of their
hands to stop sunspots.

Solbec runs a devil's apple farm on a 6 ha property, 40 km south of Perth.
The perennial flowering plant is grown, harvested and transported to a plant
where the glycoalkaloids are extracted.

Solbec outsources the final stages of the manufacturing process to reduce
infrastructure costs by sending the glycoalkaloids in powder form, and
roughly 99 per cent pure, to be further processed in Melbourne. The
glycoalkaloids are split, then re-blended to improve the purity. One acre of
land (0.4 ha) can provide enough fruit to make 80,000 doses a year.

The next year of production will include supplying doses for the national
trials. Sparling said patients will be administered coramsine on a cycle of
five days on and nine days off, receiving one injection a day directly into
the largest vein in the body. Most patients are in their 50s and 60s.

Coramsine also is being applied in a parallel study of terminally ill
patients in Western Australia under the Therapeutic Goods Administration's
Special Access Scheme. The Federal Government 'compassionate use' scheme
allows patients who have tried all accepted therapies without success to
access experimental medicines not yet in the market place.

Some of the 30 to 40 cancer patients treated so far under the scheme were
given months to live, some went on to live for more than a year when given
coramsine.

Sparling said the research and development involved in proving coramsine
was, "tough, long and arduous".

"The whole biotechnology sector is struggling," he said.

"In the meantime, we are helping people. It's important we do this work. I
also think the biotechnology sector will not stay soft for good. Though the
risks can be high, there are potentially lucrative returns to be made in
this business."

Carmelo Amalfi is a freelance science writer based in Perth


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