With concerns growing that BSE, or mad cow disease, may have spread beyond the borders of Europe, an important step has been taken in Greece by a team of scientists at Thessaloniki's Aristotle University towards a future prevention of the killer disease.

Global fears

Fears over mad cow disease and human health risks resurfaced in October, 2000 after possibly infected beef hit French supermarket shelves. The latest scare sparked consumer fears across the continent, and with the World Health Organization declaring that potentially infected meat and animal feed may have been sold around the world, the problem has gone global.

Associate Professor Theodoros Sklaviadis of Thessalonikis Aristotle University, who specializes in biochemistry and molecular biology of prion diseases, says he and his team of researchers have made an important step toward preventing the illness.

Molecular research

Since 1992 the university's prion diseases group has been conducting research on the molecular nature of such ailments as mad cow disease, an ultimately fatal neurological disorder of adult cattle formally known as bovine spongiform encephalopathy (BSE), and Creutzfeldt-Jakob Disease (CJD), considered to be the diseases human form. No cure for the neurodegenerative ailments exists.

Sklaviadis explains that while its function has not been identified, there is a normal prion protein (PrP) that all humans and vertebrates have. Through an unknown mechanism, a transformation from a physiological to a pathological isoform takes place.

"This transformation results in killing the nerve cells and subjects people to Creutzfeldt-Jakob Disease, cows to mad cow disease and sheep to scrapie," Sklaviadis explains.

He said that while it is not exactly clear how it happens on a molecular level, it is a chemical reaction that happens in the nervous system.

Suspending disease's development

In their experiments, researchers' goal was to suspend the development of the disease, intervening during the proteins transformation. They applied a method that Sklaviadis said has been known for years in which the normal human prion protein is overproduced in bacteria.

"You introduce a specific gene, ie. the PrP protein, that you want to produce in large quantitiesand you let them grow and make the protein for you," Sklaviadis said.

He added that the recombined protein is then used to fish out molecules with a great chemical affinity to the manufactured one. The attempt lasted two years, but researchers finally succeeded in isolating peptides with high affinity to the prion protein.

"PrP is the molecule we want to protect," Sklaviadis said. "The isolated compounds are tested now, to check their ability to stop the chemical reaction to inhibit the development of the diseases and prevent the cell death."

But the timeframe for applying the research to prevent human deaths is undefined.

It is commonly known that it takes several years from the time you identify candidate reagents, until you would be able to use them for a routine treatment, Sklaviadis said.

Meanwhile concern is growing.

Since 1996, 81 of 87 cases of CJD identified in Britain have been fatal, as have two of three cases in France. Outbreaks of mad cow disease also have been reported in other European countries.

Originating in Britain in the late 1970s, scientists consider mad cow disease to be a mutation of a sheep disease. By the mid-1990s tens of thousands of cases of mad cow were reported in Britain each year, prompting the European Union to ban British beef exports in 1996. The restriction was lifted in 1999.

Mad cow fears resurfaced in 2000.

In recent months, meat recalls, bans of European beef imports from around the world, including Thailand and Japan, and news of human deaths and infected cows have sparked consumer panic. Italys agricultural federation has reported a 70 percent drop in beef sales.

In the midst of the current crisis, research conducted by Sklaviadis, who has served as assistant professor at Yale University after undergraduate studies in pharmaceutical sciences in Thessaloniki and graduate studies in the United States, has taken on greater significance.

"Because of the importance of the current crisis, the scientific community intensified its efforts to come up with a solution," Sklaviadis said.

With research still in the experimental stage, the Thessaloniki native said the group is currently trying to biochemically characterize all isolated compounds and test them for their activities in collaboration with other scientists abroad.

Sklaviadis' lab, consisting of at least 10 scientists and students, has participated in several national and European research projects and has active collaborations with US-based Mount Sinai Medical Center, Britain's Central Veterinary Laboratory and Imperial College and Austria's Klinisches Institut fur Neurologie der Universitat Wien.

Funding for the labs research has come from such sources as Greece's Health Ministry and Development Ministry and the European Union's Biomedical and Health Research program (BIOMED).

Sklaviadis said: "it is absolutely necessary to develop new therapies not only to prevent but also to cure transmissible encephalopathies."

"Several drugs with known activity against pathogens like CJD, BSE and scrapie are tested in vivo in animal models now," he said. "Hopefully, within the next few years we would be able to talk about therapeutic approaches towards prevention and cure."