“We were hopeful then but ever since, things have gone so much better than we expected. We have now succeeded in binding the dangerous prions and preventing them from attacking the brain cells. This could be the first step towards an effective treatment against prions,” says Peter Nilsson, professor of organic chemistry at Linköping University.
Prions spread to the brains of humans and animals via infected food. That is what happened in the 1990s during the mad cow disease outbreak. During contagion the proteins in the body take on an incorrect shape (prions) and multiply. In the end there is so much of the defective structure that small accumulations build up in the cells which then die.
Researchers tested different blends of LCP on mice infected with prions. The most promising alternative lengthened the survival of the mice by more than 80%, compared with those animals which were not injected with LCPs. Mice that got the LCP molecules before they were infected survived for 140 days, while those that were injected with molecules after the time of infection survived for 100 days. The findings were published in Science Translational Medicine.
The tailor-made molecules used in the study were produced at Linköping University.
“You can compare the molecule to a backbone along which you can change different elements to see what the effect is. Previously it was not possible to control in detail what the different molecules would be like, but now we can. With extremely small changes we have had an extremely large impact,” says Peter Nilsson.
There are similarities between prion diseases and what happens in the brain in Alzheimer’s, Parkinson’s and ALS. The researchers now hope to find a molecule that also affects these diseases in order to get closer to a cure for them in the future too.
In addition to Peter Nilsson, Per Hammarström, Andreas K. O. Åslund, Hamid Shirani, Jeffrey J. Mason and Sofie Nyström from Linköping University took part in the study.
Above right: Brain tissue from a prion infected mouse shows that nerve cells (blue) died and were replaced by empty cavities.
Above, right: In the same area of the brain, in tissue from a prion infected mouse that has been treated with the molecule, no changes can be seen. Photo: Linköping University
Picture right: Professor Peter Nilsson. Photo: Vibeke Mathiesen
Structure-based drug design identifies polythiophenes as antiprion compounds
Uli S. Herrmann, Anne K. Schütz2, Hamid Shirani, Danzhi Huang, Dino Saban, Mario Nuvolone, Bei Li, Boris Ballmer, Andreas K. O. Åslund, Jeffrey J. Mason, Elisabeth Rushing, Herbert Budka, Sofie Nyström, Per Hammarström, Anja Böckmann, Amedeo Caflisch, Beat H. Meier, K. Peter R. Nilsson, Simone Hornemann and Adriano Aguzzi.(2015) Science Translational Medicine, Vol 7, No. 299