A common antibiotic may be a useful weapon against the abnormal proteins that cause "mad cow" and other brain-wasting diseases, researchers in Italy report.
Mad cow disease, or bovine spongiform encephalopathy (BSE) as it is officially called, is an incurable brain-wasting disease in cows. More than 100 people in Europe, almost all of them in Britain, have developed a similar ailment, new variant Creutzfeldt-Jakob disease (vCJD), from eating BSE-infected meat.
BSE, vCJD and other related illnesses, such as the animal disease scrapie, are marked by the build-up in the brain of abnormal versions of proteins called prions. The abnormal prions are resistant to enzymes that would otherwise remove them, which leads to degeneration of brain cells.
There is no treatment for vCJD and other prion diseases, although several compounds do interfere with prion formation. Unfortunately, these compounds either cannot travel from the blood into the brain, cause severe side effects, or both. But a report in the online Proceedings of the National Academy of Sciences Early Edition suggests that tetracyclines, a class of commonly used antibiotics, may affect the ability of prions to cause disease.
Dr. Fabrizio Tagliavini of the Istituto Nazionale Neurologico Carlo Besta in Milan, Italy, and colleagues treated tissue samples taken from patients with vCJD and cows with BSE with the drug tetracycline. When the prions were exposed to the antibiotic, they became less resistant to digestion by enzymes. The greater the dose, the less resistant the prions became to enzymatic digestion and, therefore, removal.
After these promising results, the researchers tested tetracycline in hamsters with scrapie. When the prions were exposed to tetracycline before injection, the hamsters did not become sick until significantly later and lived longer, and this delay was accompanied by a lag in brain abnormalities that normally develop in brain-wasting diseases.
The findings suggest that tetracyclines, which are already approved for human use, could be helpful for people with brain-wasting diseases, the report notes. "Tetracyclines should be reconsidered for pharmacological effects independently from the antibiotic activity," the authors state.
Antibiotics could also have a role in preventing infections, the investigators suggest. When Tagliavini's team mixed tetracycline into a highly diluted solution containing scrapie, one third of the hamsters exposed to the solution did not develop the disease.
The results suggest that it may be possible to use antibiotics to inactivate prions in potentially contaminated products, the authors conclude.
If it "may be possible to use antibiotics to inactivate prions in potentially contaminated products," is it at all possible that antibiotic feed additives have been helping to do just that? Where would one start looking if one wanted evidence one way or the other?
Helena Spedding Deputy Editor Animal Pharm
[We are grateful to Helena Spedding for her challenging question. Indeed, the possibility that tetracyclines in cattle feed concentrates have influenced the infection rates and/or the incubation time of BSE-infected animals is a logical consequence of the researchers' conclusions. If this indeed has taken place, it would also have been dose-related, in line with the current paper's findings.
Analysing data on the feeding patterns and tetracycline use/dosage on cattle farms exposed to MBM-contaminated feed 15-20 years ago should be seriously considered, but might be a very difficult if not impossible task. Such has been the experience of several investigators in various European countries who have been trying to carry out studies related to other past feed practices, in order to analyse the possible role of animal fat and gelatin (in calf-milk substitutes) in the epidemiology of BSE in several (continental) EU countries as well as BAB (born after ban) cases in the UK.
Another approach might be a prospective one, namely experimental oral challenge trials in cattle with BSE-contaminated concentrates, with and without tetracycline. The need for such trials might be raised and considered in light of the epidemiological investigations, when completed.
They might, though, remain on paper in view of the costs, the large number of animals required, and the necessary duration of such trials.
The 2 scientific bodies that might be engaged in discussions on the issue are SEAC (Spongiform Encephalopathy Advisory Committee, UK) and SSC (the European Scientific Steering Committee). Both are permanently following epidemiological data and new relevant scientific developments. They will study the the current paper and may eventually recommend further research or operational steps.
The abstract of the paper "Tetracyclines affect prion infectivity", by Gianluigi Forloni et al. can be seen at the Pharmacology section of PNAS posting of 29 Jul 2002:
[I note that "When the prions were exposed to tetracycline before injection, the hamsters did not become sick until significantly later and lived longer." The authors have apparently not yet shown any in vivo effect of antibiotic administration *after* infection, which is what we want to see.:
