How to Treat Prion Diseases
Scientists are stumped as to the development and nature of proteinaceous infectious particles. Neither virus nor bacteria, these prions, are believed to cause transmissible spongiform encephalopathies (TSE), rare diseases said to be 100% fatal, without possessing nucleic acids. Their unhindered growth is thought to be the cause for bovine spongiform encephalopathy (BSE), or Mad Cow Disease, Creutzfeldt-Jakob (CJD), scrapie and other TSE, diseases characterized by the brain microscopically turning into sponge-like matter. There are no cures or effective treatments available today because drawbacks constantly prevent the development of efficient therapy. Studies continue to slowly progress, hoping to find methods to immunize against more prion diseases.
No one presently has a solid understanding as to why TSE, or prion diseases, occur. The simple explanation is that PrP(c), the normal isoform of the prion protein, is forced to fold into PrPSc, the other pathological isoform, causing the misfolded PrP(c) to acquire protease-resistance. As to a physical presentation, a clumped protein consisting primarily of alpha-helices (spirals) is converted into one consisting primarily of beta-sheets (sets of pleated hairpins). In an essence, alpha-helical content decreases while beta-sheet content increases. The newly converted protein then possesses the same characteristics as those of the native PrPSc (Korth, Streit, & Oesch, 1999).
PrPSc acquires partial protease resistance upon the transformation and passes this resistance along to the naturally protease-sensitive PrP(c). Protease is an enzyme that breaks down proteins or peptides, deeming the protease-sensitive proteins soluble; so during the conversion, both PrPSc and the morphing PrP(c) increase in insolubility. Without the aid of the natural enzyme or some other form of treatment, there is little able to prevent a complete invasion of the mutated prions, which is why prion diseases are said to be 100% fatal, as rare as they are (Korth et al., 1999).
Possible Solutions: Methods
Since PrP(c) is not shown to be necessary for any major biological function, the obvious solution is to reduce the expression of that isoform. Mentioned earlier, PrPSc needs PrP(c) to multiply. It would then make sense if the reduction of the good isoform also reduced the spread of the disease. This method could be achieved by “altering the regulation of PrP gene expression or by using modern techniques of gene therapy,” meaning the use of antisense oligonucleotide, RNAi, or of genetically engineered ribozymes (Soto, 2006, p. 103). The effectiveness of such method, however, is still yet to be determined.
Another root lies in the interaction between PrP(c) and PrPSc. In vivo, the first step of the conversion is the binding of the two isoforms. Preventing the two from joining means preventing prion replication from occurring (Soto, 2006). Peptides, comprising linear sequences...