Tetracyclines show significant activity against prions

According to a group of European scientists, tetracyclines can reduce prion contagiousness by inhibiting the conformational conversion of the normal cellular protein PrP to an infectious prion (PrPSc) resistant to proteolytic dehydration.

In an article published in the August issue of Proceedings of the National Academy of Sciences, Dr. Fabrizio Tagliavini and staff at the Instituto Neurologico Carlo Besta, Milan, claim that tetracyclines can be the drug of choice for prion-induced encephalopathies. for the inactivation of prions in potentially contaminated products. In addition, they can be used in the development of preventive measures against this group of diseases.

Scientists incubated brain tissue affected by a new variant of Creutzfeldt-Jakob disease (CJD) or bovine spongioform encephalopathy (BEC), with tetracycline and doxycycline. This led to a decrease in resistance to proteases, accompanied by a decrease in the contagiousness of prions, and the degree of decrease in resistance depended on the dose of the drug.

Additional experiments have shown that hamsters who have received an intracerebral injection of cerebral homogenate affected by spongioform encephalopathy and pretreated with tetracycline have shown a significant delay in the manifestation of clinical symptoms and an increased life expectancy compared to animals inoculated with prions which have not been pretreated with tetracycline.

In addition, there has been a delay in the manifestation of magnetic resonance disorders in the thalamus, neuropathological changes and accumulation of PrPSc.

When researchers introduced a highly diluted brain homogenate into hamsters, affected by spongioform encephalopathy and treated with tetracycline, a third of the animals did not develop the disease at all. According to scientists, this finding is particularly important with regard to acquired forms of prion disease, such as iatrogenic CJD, a new version of CJD and SEC, developing after contact with organic materials, probably containing a low number of prions.

A group of scientists led by Dr Tagliavini believes that the pharmacological role of tetracyclines should be reviewed, given their activity not only as antibiotics. In addition, in addition to their possible use in the treatment of prion diseases, tetracyclines have therapeutic potential for use in neurodegenerative diseases caused by poor protein accumulation.