March 24, 2002 Philadelphia Inquirer by Faye Flam(KRT) - Is the human version of mad cow disease a ticking time bomb that will eventually kill more than 100,000 people, or has it run its course by killing just 120?
Millions of Europeans and tourists may have been exposed to the deadly brain disease by eating the beef from infected cattle. But the disease can take years or even decades to show up in its victims, so medical researchers know they may be in a race against time to find a treatment.
It all depends on the incubation time, which could exceed 20 years.
"Millions of people in Europe could have been exposed," said Anthony Williamson, a neurologist studying the disease at the Scripps Research Institute in La Jolla, Calif. "It's not clear how many people are walking around with the disease that will manifest it at a later time," he said.
The first cases appeared in Britain in 1995, and since then, several have cropped up in France, Ireland, and Italy. Infected cattle have been identified in a number of European countries and, more recently, Japan.
There is no evidence the disease has affected American cattle, and no one has fallen ill from the human version of mad cow disease in the United States, with the exception of one Briton who came to this country seeking treatment, said Lawrence Schonberger, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta.
The human version of the disease often starts with psychiatric symptoms - anxiety and depression - before progressing to memory loss and coordination problems. Patients die within about 14 months. Several drugs are under development.
Epidemiologists are scrambling to find patterns that could help explain why certain people have been stricken and not the millions of others who probably also consumed meat from infected animals.
Estimates vary on the danger to Europeans and Americans who traveled in Europe, especially Britain, during the 1980s and early 1990s - the time when infected animals were part of the food supply. Some say that only a few hundred will die, others predict more than 100,000.
Schonberger at the CDC is still actively engaged in surveillance efforts, doing autopsies on any suspicious cases in the United States. Nearly all the people he's examined have turned out to have a related disease, Creutzfeldt-Jakob Disease (CJD), which generally strikes older people and is not connected to tainted meat. About 300 people in this country die from CJD every year. The cause in most cases is unknown, though some are linked to genetic predisposition, and the disease can be transmitted by infected corneal transplants or tainted brain-surgery instruments.
The human form of mad cow disease is called new-variant CJD, which leads to some confusion, said Schonberger.
The reason new variant CJD has been so difficult to diagnose and treat is that it's so different from almost any other infectious agent. Mad cow disease and its human form are caused by something called a prion, which, unlike a bacteria or a virus, is not a living thing but simply a molecule - a protein - that takes on a deadly shape.
That makes it hard to destroy.
To make matters more complicated, people and animals all carry prions in their brain cells, which, in healthy form, come in a twisted, spiral shape. The infected cows carry a different form of this same protein, chemically identical but shaped in a more sheetlike configuration.
It appears that when people eat meat from infected animals, some of the misshapen proteins can work their way into the brain, where they start to convert the healthy brain prions into their own deadly form.
Once infected, the brain develops spongelike holes.
Biologist Stanley Prusiner of the University of California, San Francisco, said he's looking at ways to prevent the abnormal prion from doing its dirty work of converting the normal ones. Prusiner, who won the 1997 Nobel Prize for discovering prions, explained his work in a talk recently at the University of Pennsylvania.
Two drugs appeared to halt prion conversion in cells culture: quinacrine, which is approved for treating malaria, and chlorpromazine, approved for schizophrenia. Last July, Prusiner and colleagues decided to try the drugs on victims of the human version of mad cow disease who were near death. Though the drugs had not been tested against this disease in animals, it was the only hope for these patients.
The first patient with mad cow disease who was treated with quinacrine was 20-year-old Rachal Forber of Merseyside, England. By the time she started the treatment she was confined to a wheelchair and was unable to speak or to feed herself. Soon after starting the drug, her parents reported that she regained some ability to speak, to walk and to use a knife and fork. But she died last December of liver failure, possibly a side effect of the drug.
Some scientists are continuing to study these drugs, said Jiri Safar, a neurologist at the Institute of Neurodegenerative Diseases at the University of California, San Francisco. "We want to synthesize a better molecule that would be more efficient in treating this disease," he said. "We're also looking at new compounds that are less toxic."
Such drugs, he said, are probably going to end up working best in patients still in early stages of the disease. Or they may prevent the illness only in those who were exposed but remain symptom-free.
Currently, there's no way to know who has been exposed to mad cow prions, said Scripps researcher Williamson. The only way he and other researchers can identify the disease definitively is postmortem, by examining the brain.
A blood test could prevent thousands more cases by allowing people in Britain to screen the blood supply, he said. People who might have been exposed through British beef are not allowed to give blood in the United States, but the British cannot afford to stop adding to their blood supply, he said.
Williamson and most others seeking a test are looking at antibodies, which are now used to detect proteins in a number of tests, including pregnancy tests.
"Williamson has been studying an antibody that might attack the errant prions, making it a potential treatment.
Meanwhile, others have been trying to sleuth out patterns in the way the disease has struck in Europe. The average age of its victims is 28 - surprisingly young. No one knows why.
There also appears to be a genetic predisposition to getting sick. The normal version of the prion protein is associated with a gene that all people carry. That gene comes in several varieties, and only one type so far has been found in all 120 or so victims. That type is carried by about 40 percent of Europeans and 12 percent of Japanese.
However, it may be that people with the seemingly protective form of the gene are simply able to incubate the disease longer.
Whether many more people die will depend, therefore, on how fast the epidemic grows and how fast scientists can come up with tests and drugs. So far, the situation doesn't look as dire as the worst-case scenarios of several years ago, CDC's Schonberger said.
"It's not exploding, but it's still there," he said. "Cases are still accumulating and we don't have any clear evidence that we've peaked."