In a discovery that could potentially help millions of people around the world, researchers have determined how the SARS virus leads to acute lung failure in lab animals and devised a way to reverse the often deadly condition.
SARS, or severe acute respiratory syndrome, killed 774 people - including 44 in Canada - and sickened almost 8,100 in 2003. Outbreaks in 29 countries threw public health systems into chaos, disrupted international travel and hammered local economies.
Now researchers from Canada, Austria and China say they have discovered what makes the disease so potentially lethal - at least in laboratory mice. And learning that cause may lead them to a treatment for humans, they report in this week's issue of the journal Nature Medicine.
Furthermore, the significance of the discovery extends far beyond SARS, providing a possible means of preventing lung failure from other killer diseases - including sepsis (blood infection), anthrax and avian flu, the agent that many infectious disease experts believe will launch the next pandemic.
"Acute lung failure is a disease which affects millions of people and there's no treatment," said principal investigator Dr. Josef Penninger, head of the Institute of Molecular Biotechnology in Vienna.
"People who have acute lung failure, these people are basically drowning to death in their own fluid. It's a horrible death."
The team led by Dr. Penninger, who left Toronto's Princess Margaret Hospital two years ago to head the Vienna institute, determined that the SARS virus uses a protein on cell surfaces as its window of invasion.
That protein, called ACE2, plays a role in blood pressure regulation. But the researchers believe they have unlocked another critical role.
"It turns out that this key that SARS is using to enter our body is actually very, very important to protect from acute lung failure," Dr. Penninger said from Beijing, where he was visiting Chinese scientists who collaborated on the research.
The team began by infecting lab mice with the SARS corona virus. The resulting drop in ACE2 caused their lungs to fill with fluid, triggering acute lung failure in the tiny animals.
Armed with their new knowledge about how SARS operates, the researchers theorized that if a lack of ACE2 causes lung failure, then restoring it should halt the process - and that's what they did.
They injected the mice with bioengineered ACE2, which shut down the SARS-induced lung damage.
About one million people worldwide are afflicted with acute lung failure each year and up to half of them die. Among its victims are newborns who aspirate substances into their lungs during birth and patients being treated in intensive care units.
So in a strange scientific twist, the SARS epidemic that caused so much distress and did so much damage may actually turn out to have far-reaching benefits, Dr. Penninger said.
"By revealing its secrets to us, SARS might have shown us the medicine for previously untreatable diseases."
The next step will be to find funding to develop an ACE2-based medication for humans, which he predicted could be ready for testing in people within two to three years. Because ACE2 works in the bloodstream, it could easily be administered through intravenous injection, he added.
But in a commentary accompanying the study, John Nicholls and Malik Peiris of the University of Hong Kong caution that SARS "infection in mice does not produce the typical (lung damage) picture seen in human disease."
Still, they suggest the potential of recombinant, or bioengineered, ACE2 for acute lung injury arising from viruses and other causes is worth investigating.
"This is particularly relevant as we prepare to confront a potential avian flu pandemic, armed with only a limited number of therapeutic options," they write.
Dr. Arthur Slutsky, vice-president of research at Toronto's St. Michael's Hospital and a co-author on the paper (providing expertise on lung injury), called the research findings "a major first step."
But he said it's a big leap from mice to humans, and what works in lab animals doesn't always hold true for people.
"ACE2 is found in humans and there's reason to believe it is important in humans, but clearly we would want to have human studies to be able to prove it more definitively."Report Typo/Error
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