How to Protect Against Problematic Prions


11 May 2015

If you watched news bulletins in the 1980s and 1990s, you will be instantly familiar with Bovine Spongiform Encephalitis (BSE or ‘mad cow disease’) and its human equivalent, variant Creutzfeldt-Jakob Disease (vCJD).

Triggered by abnormal proteins called prions, these distressing and ultimately fatal conditions not only caused human misery and economic loss, they were also scientifically puzzling.

Yet while BSE no longer hits the headlines as frequently, prion diseases haven’t gone away, explains UCD researcher Dr Hilary McMahon from the UCD School of Biomolecular and Biomedical Science and UCD Conway Institute, who is developing a deeper understanding of these confounding proteins and how to stop them from causing problems.

Unlike the more familiar territory of bacteria, fungi and viruses that cause communicable diseases, prions have an unusual way of working: they are effectively ‘normal’ proteins in the brain, but if they become misshapen or ‘abnormal’, they can directly trigger a prion disorder that damages the brain.

And even the ‘normal’ prion can still cause problems: it is thought to trigger other proteins to build up and cause problems in Alzheimer’s disease.

Dr McMahon’s work on the biology of prions is unravelling the complex biochemistry of this role. “We have unearthed a new pathway of control between the prion protein and the regulation of Alzheimer’s,” she says.

Her research has also identified a role for the hormone oestrogen in the development of prion disorders triggered by the abnormal prion protein. “We recently identified oestrogen levels as being a factor in whether or not a prion disease will occur,” she says.

Yet while the incidence of full prion disorders in humans is rare, we still need to be vigilant, according to Dr McMahon, who explains that a small number of people carry the abnormal prion but show no symptoms. “We have to always be aware that the agent is still out there and has the potential to be transferred on to others, as has happened during hospital procedures,” she says.

To help quench abnormal prion proteins before they can be passed between humans or into the food chain, Dr McMahon has been developing a new, enzyme-based approach to destroying the prion structure.

“The abnormal prion protein is very resilient to the standard methods that are used to sterilise hospital equipment,” she says. “So we have developed enzymes called proteases that degrade the abnormal prion proteins under very mild conditions.”

The sterilising procedure could be applied not only to hospital equipment but it could also potentially stop abnormal prions from entering the human food chain, she notes. “You may be able to spray the enzyme on fields or farms and the hope will be that it will break down the prion where present.”

And it’s important that we continue to tease out the basic biology of prions, which are still relatively new to science, notes Dr McMahon. “It’s only in the last 10 or 20 years that the research in this area has been really strong, prompted by the BSE crisis, and we have a lot left to find out about even the basic functions of the prion protein.”

Dr Hilary McMahon, Lecturer from the UCD School of Biomolecular and Biomedical Science, was interviewed by freelance journalist Dr Claire O'Connell.