Hadassah team identifies 'mad cow' protein

Hadassah team identifies 'mad cow' protein

July 2, 2001 The Jerusalem Post by Judy Siegel

A Hadassah-University Hospital research team has discovered that the prion (protein particle) responsible for the fatal "mad cow disease" in animals and Creutzfeldt- Jakob disease in humans can be detected in urine.

The tiny pathogen that causes the incurable neurodegenerative disease bovine spongiform encephalopathy (BSE) and its human variant can be identified even before symptoms appear. This means that blood donations by human carriers can be prevented, and millions of unaffected cows will be saved from wholesale slaughter.

The groundbreaking article on the discovery has just been published in the Journal of Biological Chemistry by Dr. Ruth Gabizon of the neurology department at the Ein Kerem hospital and her team of Gideon Shaked, Yuval Shaked, Zehavit Kariv, Michele Halimi, and Inbal Avraham.

The only known component of the prion, known as PrPSc, is found mostly in the brains of animals and humans affected with prion diseases, and has not been detected in blood. But the researchers demonstrate that a substance called protease-resistant PrP isoform can be detected in the urine of infected hamsters, cattle, and humans.

Gabizon said yesterday the most important thing is that "the PrP isoform was also found in the urine of hamsters inoculated with prions long before the appearance of clinical signs." Over 100 people have died in Europe, mostly in England, in recent years after eating beef infected with BSE, and many more are expected to fall victim to it, as the disease can be carried for decades before symptoms appear.

The disease was first discovered in England in 1985. Cows contracted the disease after eating feed made from sheep infected with scrapie. Since then, millions of cows have been destroyed in England and some other European countries, nearly wiping out their cattle-raising industry. Although it has not yet been proven that blood from people who carry Creutzfeldt-Jakob disease can pass the human variant on to others in infusions, the possibility has raised much concern.

Gabizon said that almost no one has looked at the urine for prions because it was thought prions did not pass through the kidneys.

Since last September, Gabizon and her doctoral student Shaked had been looking for other substances in hamster urine. They identified the tiny protein particles, and found that they do not break down in the kidneys but are eliminated in the urine.

Gabizon and her team are in the final stages of establishing a Jerusalem start-up under the auspices of Hadassah's research and development arm Hadassit to produce a commercial kit for testing animal and human urine.

So far, BSE has been easily diagnosed using urine taken from over 50 British cows diagnosed with BSE and sent to Israel, along with samples from healthy cows, by the Veterinary Laboratory Agency. "In the blind test, we quickly picked out the affected animals," Gabizon said.

A decade ago, Gabizon worked in the lab of Prof. Stanley Prusiner, the American discoverer of the prion who recently received the Nobel Prize for Medicine for the achievement. Since she returned to Hadassah, she has dedicated her time to work on prions.

Currently, people who have spent even a short time in England are barred from donating blood. However, when the urine test becomes available, this sweeping restriction will most likely be dropped.

Gabizon said the Hadassah discovery also raised the "alarming possibility" that the human and animal forms of the disease can be transmitted by contact with infected urine, even from those who as yet show no symptoms.

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