Scrapie, Creutzfeld-Jakob and BSE are among the most unusual diseases known to medical research. Unusual because the pathogens are apparently neither viruses nor bacteria, being simply protein molecules known as protein prions. What is even more peculiar: exactly the same prion proteins occur in healthy animals. The only difference is that they have a different shape. When there is contact with their ‘diseased twins?they change their shape, also becoming ‘diseased.?The result is an irresistible chain reaction. The malformed prion proteins can be deposited in the brain, thereby destroying brain tissue. Prion diseases are always fatal, often, however, not until months after the outbreak of the disease. As yet there is no cure.
In mice suffering from scrapie the pathogenic prion protein is known as PrP-Scr, whereas the normal variant is PrP-C. PrP-C seems to have a protective effect in diseases like a stroke. Interestingly, mice which cannot produce any PrP-C appear to be completely healthy. This has become the starting point for a new therapeutic approach which for some years now has been current in research circles: can we not simply switch off the production of ‘healthy?PrP-C in infected animals, thereby depriving the ‘di seased?PrP-Scr of its ability to spread" In this way the chain reaction would be interrupted.
New therapeutic approach
Scientists from Munich’s Ludwig Maximilian University and the University of Bonn, in conjunction with colleagues from the Max Planck Institute in Martinsried, have been testing whether this approach works. In doing so they cut back the production of PrP-C in mice by means of an ingenious procedure. The researchers used a special RNA molecule for this purpose. RNA is related to the genetic molecule DNA. There are types of RNA known as siRNAs which can attach themselves to specific genes, thereby preventing these from being ‘read? The production of the appropriate protein is thus shut down. This effect is known as RNA interference; its discovery was rewarded with this year’s Nobel Prize for Medicine. “We modified the brain cells of mice in such a way that they were able to produce siRNAs in place of the ‘healthy?PrP-C protein,?explains Professor Alexander Pfeifer, director of the Institute of Pharmacology of the University of Bonn. “In cell cultures the production of PrP-C was thereby cut back by up to 97 per cent.?
The researchers then tested what effect these siRNAs had on mice which had scrapie. ‘If brain cells are to produce siRNAs, you have to smuggle in the corresponding gene,?says Professor Kretschmar, director of the Prion Centre of Munich’s Ludwig Maximilian University. ‘But presumably we’ll never manage to equip all the cells in the brain with this gene.?This is why the researchers also wanted to find out how many cells they have to ‘revamp?genetically to treat scrapie or similar diseases successfully. For this purpose they bred mice that only had some brain cells which could produce siRNAs. ‘Whereas the untreated mice died on average after 165 days, the mice which had been treated lived appreciably longer,?is how Professor Kretschmar summarises the results.
It varied ho w much longer they lived: if only a few cells could produce siRNAs, the mice died at almost the same time as the control mice, i.e. on average after 170 days. However, if the majority of the brain cells were protected by siRNA, the mice survived the prion disease for up to 230 days, in other words about a third longer.
‘Basically siRNAs seem to be a promising therapeutic option for scrapie, CJD or BSE,?Professor Pfeifer emphasises. ‘However, it will take years before the method can be used on human beings.?The method is also relevant for animal breeding: in principle it can be used to breed cattle which cannot produce any PrP-C. They would then be resistant to BSE.
Source:University of Bonn
Related biology news :
1. Weizmann Institute scientists develop a new approach for directing treatment to metastasized prostate cancer in the bones.
2. MSI releases moleculizer - a new approach to simulation of intracellular biochemical networks
3. Stopping smallpox in its tracks: A new anti-viral approach
4. Building a protein name dictionary from full text: a machine learning term extraction approach
5. Rensselaer researchers develop approach that predicts protein separation behavior
6. Huntingtons cure in flies lays groundwork for broader treatment approaches
7. Results of worlds first gene therapy trial for arthritis show approach safe, feasible
8. Vaginal gel may provide a new approach to HIV prevention
9. Clinical trial to test stem cell approach for children with brain injury
10. Study in Science holds promise for a new approach to drug therapy
11. U-M researchers take new approach to defeating Gram-negative bugs