Spongious encephalopathy (1920–2010)

U radu se istražuju prve prionske bolesti od kojih je većina genetskog podrijetla. Uključuju točkaste mutacije (promjena jedno baznog para, change in a single base pair Adenine/Guanine, Thymin/Cytosine) DNA, insercija oktapeptida u N-ti dio prionskog proteina (3 do 216 oktapeptida), delecije (samo dva ili tri su poznata do sada). Tri ili više insercija potrebna za ovu bolest. To je 35 točkastih mutacija (najčešće su na kodonima 102, 178 i 200). Najnovija varijanta CJB, koja nastaje konzumacijom mesa zaraženog goveda, karakterizira polimorfizam Metionin/Metionon (M/M) na kodonu 129 u 98 posto slučajeva. U ostalih oblika prionske bolesti nema zabilježenih promjena u prionskom genomu. Točkaste mutacije karakterizira jedna promjena u jednom baznom paru od 109 postojećih u ljudskom genomu. Genetske prionske bolesti čine 10-15 posto svih slučajeva prionske bolesti. Ne-genetske prionske bolesti čine 85-90 posto slučajeva, a zajedno se javljaju u 1,5-2,5 slučaja na milijun stanovnika. Genetske prionske bolesti su istovremeno i infektivne. Patološki prionski protein (PrPSc) potreban je za postavljanje dijagnoze. Klinička dijagnoza genetskih i ne-genetskih prionskih bolesti čini se vrlo kompliciranom. U bolesnika s genetskim prionskim bolestima ponekad postoje anamnestički podaci o sličnim slučajevima koji su se pojavili u ovoj ili prijašnjim generacijama. Genetske prionske bolesti mogu se dijagnosticirati analizom baznih parova laboratorijskom metodom ili automatskim uređajem ili citokemijom, metodom lančane reakcije polimerazom, Western blot metodom, imunoenzimskim testom (ELISA). Za izvođenje ovih metoda potrebno je konstruirati tzv. „primere“ ili početnice za kodone 102, 178 i 200. Rade se i obdukcije, biopsije, elektroneurodijagnostika i analiza cerebrospinalnih markera prionskih bolesti. Diferencijalna dijagnostika na druge bolesti je također vrlo važna. Najviše publikacija objavio je Prusiner, koji je dobio i Nobelovu nagradu. On je nedavno promijenio svoje mišljenje o eliminaciji proteina X i prihvatio tezu o utjecaju stranih čimbenika. Patološki prionski protein PrPSc ne može nastati iz prionskog proteina PrPC jer PrPSc, kao protein, ne može stvarati nove proteine. PrPSc je proizvod gena, što znači da je nukleoprotein. U radu smo sažeto prikazali njegove ideje o genetskim prionskim bolestima. Infektivnost genetskih i ne-genetskih prionskih bolesti čini se vrlo niska. U posljednjih 40 godina analizirana je kultura tkiva: mnogo puta je bila pozitivna i uzročnik je mogao proći “pasaže”. Godine 2007. objavljen je rad o virusnoj etiologiji prionskih bolesti. Međutim, mnogi sojevi otkriveni do danas mogli su se uspoređivati samo elektronskim mikroskopiranjem. Pronađene su čestice veličine 20 do 50 nanometra, koje su se smatrale virusima, ali usporedba nije bila moguća. Nekoliko drugih neurotropnih virusa također je detektirano, čime se zakomplicirala dijagnostika prionskog uzročnika. Potrebna su daljnja istraživanja kulture tkiva, što je razvidno iz brojne do sada objavljene literature.We have studied the first prion diseases of which most cases were of genetic origin. They include point mutations (change in a single base pair Adenine/Guanine, Thymin/Cytosine) in the DNA, insertions of octapeptides in the N-part of the prion protein (3 to 216 octapeptide) and deletions (only two or three have been known until now). Three or more insertions are needed for the disease. They are 35 point mutations (the most frequent are at codon 102, 178 and 200). The newest variant CJD, which is caused by eating infected meat from infected beef is characterized by polimorphism Methionine/Methionone (M/M) at codon 129 in 98 percent of cases. The other cases of prion disease have no change in the prion genome. Point mutations are characterized by a single change in one base pair of 109 available in the human genome. Genetic prion diseases make up to 10-15 percent of all prion disease cases. Non genetic prion diseases are 85-90 percent; they together make up to 1,5-2,5 per million of inhabitants. Genetic prion diseases are simultaneously also infectious. PrPSc is needed for the diagnosis. Clinical diagnosis of genetic and nongenetic prion diseases appears very complicated. Genetic disease has sometimes anamnestic information on similar cases appearing in this or earlier generation. Genetic prion disease can be diagnosed by the study of base pairs by a laboratory method or by an automatic device or by Cytochemistry, Polymerase chain reaction, Western blot, Enzyme immunoassay (ELISA). Genetic methods need primers for the codon 102, 178 and 200. There are also autopsy, biopsy, electroneurodiagnostic and substances in the cerebrospinal fluid. The differential diagnostic to other diseases is very important. Most publications are from Prusiner, who received the Nobel prize. He changed recently his mind in eliminating the protein X and accepted clearly effects of foreign factors. PrPSc cannot originate from PrPC because both are proteins. The PrPSc is a product of the gene, i.e. that means it is nucleoprotein. We have summarized his ideas on genetic prion disease in the text. The infectivity of genetic and nongenetic prion diseases appears very low. The last 40 years tissue culture was tried: they were many times positive and the agents could be passaged. In 2007 a publication appeared as the virus of prion diseases was found. But many strains detected until now could only be compared with electron microscopic appearance. 20 to 50 nanometer great formations were found but the tissue itself did not function and a comparison was not possible. Several other neurotropic viruses were also found and this complicates the diagnosis of the prion agent. The tissue culture studies should be helped as evident from numerous publications in the world literature