Scientists race to stop mad cow threat: Test sought to detect fatal brain disease that may be carried in blood

Scientists race to stop mad cow threat:
Test sought to detect fatal brain disease that may be carried in blood

June 25, 2001 The Ottawa Citizen by Melanie Brooks

Under the looming threat of a worldwide outbreak of mad cow disease, Health Canada and independent scientists are racing to find ways to protect the nation's blood supply.

Scientists are unsure whether Variant Creutzfeldt-Jakob Disease (vCJD) can be transmitted by blood, and without a test to identify infected people, there is a "theoretical risk" to the nation's blood supply, says Dr. Graham Sher, vice-president of medical, scientific and clinical management for the Canadian Blood Services.

"Getting vCJD from a blood transfusion is still a theoretical risk. But the risk of transmission is there," says Dr. Sher.

Variant Creutzfeldt-Jakob Disease is a fatal neurological disorder that has affected more than 100 people to date, mostly in Britain, who were likely infected by eating beef tainted with mad cow disease.

The only ways to protect against the potential spread of disease through the blood system are to develop a blood test or ban people who have lived in affected countries from donating blood.

Neil Cashman, a scientist at the Centre for Research and Neurodegenerative Diseases at the University of Toronto, is one of an elite handful of scientists around the world racing to come up with a test for vCJD. Some of the scientists are amongst the very best in the world, like Stanley Prusiner, who won the Nobel Prize in physiology in 1997.

"The other problem with this is we don't know how many people are going to be affected," says Dr. Cashman. "If you run the numbers, it's anywhere between a few hundred and a few hundred thousand. And obviously, a few hundred thousand would be a disaster of the first magnitude.

"There is definitely a heightened interest in finding a test and protecting the blood supply. We need to find a test, and I think we'll have it within a year."

In Canada, Mr. Cashman does research for Caprion Pharmaceuticals, a small biotech company in Montreal. The company collaborates with two other research laboratories in the United States to find a blood test for vCJD. But the complicated way in which the disease affects the brain is making it difficult, he said.

"The disease is caused by an infectious agent which is unlike anything that we know," says Mr. Cashman.

The disease affects isoforms, or protein groupings, in the brain called prions. In their normal form, prion proteins are present in every human brain and serve a normal function.

But vCJD causes the prions to refold into an abnormal form. This mutated prion then acts as a template for other prions, which then in turn refold into the harmful, abnormal form.

So far, the only way scientists can detect this mutation is through samples of brain tissue taken during an autopsy after the infected person dies. But the test used on brain matter isn't sensitive enough to detect problems in blood.

"In the brain, there can be billions of infectious prions per gram of tissue. So that's easy to detect, using a test called protease resistance," says Mr. Cashman.

"However, in the blood, there are may be only dozens or hundreds of units of infectivity per millilitre. So the test we use to find prions in the brain is not sensitive enough to find them in blood.

"In addition, prions do not have a nucleic acid like DNA or RNA, so the tools we use to detect viruses we can't use. So it'sbeen a real puzzle to try to detect prions in blood."

To get around this, Dr. Cashman and others are trying to boost the sensitivity of the brain test, or develop another test that can single out infectious agents in a blood sample.

This month, scientists in Switzerland and Britain made breakthroughs in these areas, but are still unsure how much more sensitive the test needs to be to detect prions in blood.

The sooner the test is developed, the better, says Dr. Cashman.

Although it's unproven, there is evidence to suggest vCJD can be transmitted through blood products.

"That is the $64,000 question," says Dr. Cashman. "There is a great deal of concern and some scientific rational for thinking vCJD might be transmitted through blood.

"There's no human case we can point to now and say, 'Aha, it's transmitted through blood.'

"But animal experiments in mice and in sheep seem to suggest that vCJD can be transmitted through blood and blood products."

At an international conference in Paris last week, experts warned of a vCJD pandemic similar to the emergence of AIDS 20 years ago. Like AIDS, vCJD kills. There is no cure.

Earlier this month, the Citizen obtained a Health Canada report saying vCJD could already be in Canada, incubating in unsuspecting Canadians. To date, there have been no reported cases of vCJD in Canada.

"The incubation period for vCJD could be more than 20 years," says Dr. Cashman.

"It means there are probably lots of people walking around who are incubating the disease, and because there's no test for it, we don't know who they are."

In the meantime, the only thing that can be done to prevent the theoretical spread of vCJD is to ban donors who have lived in BSE-infected countries from donating blood.

Right now, Health Canada restricts people who have spent more than six months in Britain or France from 1980 to 1996 from donating.

But with recent reports of cases emerging in France, Ireland, and Hong Kong, the agency is considering whether to extend its ban to other European nations.

The bans on Britain and France, implemented in 1999 and 2000, reduced the potential risk of vCJD entering the blood system by about 75 per cent.

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