Physicists Propose Mad Cow Strategy

Physicists Propose Mad Cow Strategy

NewsMax.com Wires
Monday, March 26, 2001

DAVIS, Calif. – A team of biophysicists at the University of California, Davis, has proposed a controversial treatment for disorders such as mad cow disease and its human version, Creutzfeldt-Jakob disease.

Led by physics professor Daniel Cox, the scientists suggest that by exploiting a unique quality of these prion diseases – prions, the infectious agents, do not infect all species equally – researchers could inject normal prions from one species to inhibit formation of abnormal prions in another species.

Caused by infectious, deformed proteins called prions, the neurological diseases encompass a wide array of troubling, mysterious spongiform encephalopathies, so named because they frequently cause the brain to become riddled with holes.

Dr. Stanley Prusiner originally characterized these diseases in 1982. The University of California, San Francisco, neurologist discovered that mammalian cells contain prion proteins of two types: normal, cellular prions that don't cause disease and abnormal, misshapen prions that arise from normal prions and do cause disease. Prusiner was awarded the Nobel Prize in Physiology or Medicine for his prion work in 1997.

Prion diseases exhibit an unusual quality called species asymmetry. For instance, while diseased mice infect hamsters easily, diseased hamsters infect mice poorly. Cox of UC-Davis uses a computer to simulate this asymmetry.

Using hamsters and mice as one example, he claims the simulation shows that normal hamster prions, if injected into a mouse with prion disease, will significantly slow the disease in the mouse. The normal hamster prions actually block further formation of abnormal mouse prions, he asserts.

Other proposed therapies have included blocking the genes that give rise to unwanted prions and preventing prion propagation altogether, according to Dr. Susan Lindquist, Albert Lasker Professor of Molecular Genetics and Cell Biology at the University of Chicago.

"But I haven't heard that normal prions from one species might interfere with the disease process in another," Lindquist told United Press International. "That's a new idea."

Dr. Peter Lansbury, a neurological chemist and leading prion researcher at Harvard University, believes Cox's protocol may be flawed.

"It is true that normal hamster prions will probably inhibit conversion of normal mouse prions to their abnormal form," Lansbury told UPI. "The problem is, the normal hamster prions will also be converted – to abnormal hamster prions – in the process."

Cox, however, argues that abnormal hamster prions are actually a necessary part of the process. In the mouse, they significantly reduce the formation of abnormal mouse prions. They also won't cause disease in mice, Cox argues, because of the species asymmetry – abnormal hamster prions infect mice poorly.

Lansbury remains unconvinced, but suggested a simple variation on Cox's approach that could produce the desired effect.

"A variant of normal hamster prion might be found that could block the disease in mice without producing any abnormal hamster prion in the process," Lansbury told UPI. Lansbury pointed out that treatments for sickle cell anemia are based on a similar scheme.

Dr. Fred Cohen, professor of pharmacology and medicine at the University of California, San Francisco, is pleased to see physicists such as Cox simulating the mechanisms of prion diseases.

"I would say that such simulations can be valuable in that they allow us to think about certain more qualitative biological experiments in a quantitative way," Cohen told UPI. "Cox and co-workers do an excellent job of pursuing one model under one set of assumptions."

However, Cohen is troubled that Cox's simulated treatment allows for the buildup of abnormal prions from one species in another. He believes clearing the abnormal hamster prions from the mouse, although they may slow the disease process, will be critical to the success of Cox's proposal.

"I look forward to the time when Cox and his team introduce clearance of abnormal scrapie prions in their treatment protocol," Cohen told UPI. "Increasingly, it has become clear that clearance is an important phenomenon in the biology of the prion diseases."

Until then, Cohen sees no way people would be inclined to consume beef from cows treated with sheep prions, for instance. Treatment of humans with animal prions, while plausible, is also a long way off, Cohen told UPI.

Cox's paper is scheduled for publication in Physical Review Letters later this year. Until that time, he would not comment on it.

"We realize how important these prion diseases have become and since this is a major foray for us into this area, we can't really comment until the paper is published," Cox told UPI.