56
Views
2
CrossRef citations to date
0
Altmetric
Review

Recent developments in therapeutics for prion diseases

Pages 35-59 | Published online: 18 Jan 2008

Bibliography

  • Prusiner SB. Prions. Proc Natl Acad Sci USA 1998;95(23):13363-83
  • Dearmond SJ, Prusiner SB. Etiology and pathogenesis of prion diseases. Am J Pathol 1995;146(4):785-811
  • Duffy P, Wolf J, Collins G, et al. Possible person-to-person transmission of Creutzfeldt-Jakob disease [letter]. N Engl J Med 1974;290(12):692-3
  • Bernoulli C, Siegfried J, Baumgartner G, et al. Danger of accidental person-to-person transmission of Creutzfeldt-Jakob disease by surgery. Lancet 1977;1(8009):478-9
  • Koch TK, Berg BO, De Armond SJ, Gravina RF. Creutzfeldt-Jakob disease in a young adult with idiopathic hypopituitarism. Possible relation to the administration of cadaveric human growth hormone. N Engl J Med 1985;313(12):731-3
  • Thadani V, Penar PL, Partington J, et al. Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft. Case report. J Neurosurg 1988;69(5):766-9
  • Gajdusek DC. Unconventional viruses and the origin and disappearance of kuru. Science 1977;197(4307):943-60
  • Bruce ME, Will RG, Ironside JW, et al. Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 1997;389(6650):498-501
  • Hill AF, Desbruslais M, Joiner S, et al. The same prion strain causes vCJD and BSE. Nature 1997;389(6650):448-50, 526
  • Collee JG, Bradley R, Liberski PP. Variant CJD (vCJD) and bovine spongiform encephalopathy (BSE): 10 and 20 years on: part 2. Folia Neuropathol 2006;44(2):102-10
  • Peden AH, Ritchie DL, Ironside JW. Risks of transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Folia Neuropathol 2005;43(4):271-8
  • Llewelyn CA, Hewitt PE, Knight RS, et al. Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. Lancet 2004;363(9407):417-21
  • Peden AH, Head MW, Ritchie DL, Bell JE, Ironside JW. Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 2004;364(9433):527-9
  • Trevitt CR, Collinge J. A systematic review of prion therapeutics in experimental models. Brain 2006;129(Pt 9):2241-65
  • Otto M, Cepek L, Ratzka P, et al. Efficacy of flupirtine on cognitive function in patients with CJD: a double-blind study. Neurology 2004;62(5):714-8
  • Benito-Leon J. Combined quinacrine and chlorpromazine therapy in fatal familial insomnia. Clin Neuropharmacol 2004;27(4):201-3
  • Nakajima M, Yamada T, Kusuhara T, et al. Results of quinacrine administration to patients with Creutzfeldt-Jakob disease. Dement Geriatr Cogn Disord 2004;17(3):158-63
  • Todd NV, Morrow J, Doh-Ura K, et al. Cerebroventricular infusion of pentosan polysulphate in human variant Creutzfeldt-Jakob disease. J Infect 2005;50(5):394-6
  • Rainov NG, Tsuboi Y, Krolak-Salmon P, Vighetto A, Doh-Ura K. Experimental treatments for human transmissible spongiform encephalopathies: is there a role for pentosan polysulfate? Expert Opin Biol Ther 2007;7(5):713-26
  • Prusiner SB. Prions: novel infectious pathogens. Adv Virus Res 1984;29:1-56
  • Weissmann C, Enari M, Klohn PC, Rossi D, Flechsig E. Molecular biology of prions. Acta Neurobiol Exp (Wars) 2002;62(3):153-66
  • Legname G, Baskakov IV, Nguyen HO, et al. Synthetic mammalian prions. Science 2004;305(5684):673-6
  • Silveira JR, Raymond GJ, Hughson AG, et al. The most infectious prion protein particles. Nature 2005;437(7056):257-61
  • Hundt C, Peyrin JM, Haik S, et al. Identification of interaction domains of the prion protein with its 37-kDa/67-kDa laminin receptor. EMBO J 2001;20(21):5876-86
  • Gauczynski S, Nikles D, El-Gogo S, et al. The 37-kDa/67-kDa laminin receptor acts as a receptor for infectious prions and is inhibited by polysulfated glycanes. J Infect Dis 2006;194(5):702-9
  • Vana K, Weiss S. A trans-dominant negative 37kDa/67kDa laminin receptor mutant impairs PrP(Sc) propagation in scrapie-infected neuronal cells. J Mol Biol 2006;358(1):57-66
  • Leucht C, Simoneau S, Rey C, et al. The 37 kDa/67 kDa laminin receptor is required for PrP(Sc) propagation in scrapie-infected neuronal cells. EMBO Rep 2003;4(3):290-5
  • Harris DA. Cellular biology of prion diseases. Clin Microbiol Rev 1999;12(3):429-44
  • Gorodinsky A, Harris DA. Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. J Cell Biol 1995;129(3):619-27
  • Taraboulos A, Scott M, Semenov A, et al. Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform. J Cell Biol 1995;129(1):121-32
  • Vey M, Pilkuhn S, Wille H, et al. Subcellular colocalization of the cellular and scrapie prion proteins in caveolae-like membranous domains. Proc Natl Acad Sci USA 1996;93(25):14945-9
  • Sarnataro D, Campana V, Paladino S, et al. PrP(C) association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. Mol Biol Cell 2004;15(9):4031-42
  • Bate C, Salmona M, Diomede L, Williams A. Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem 2004;279(15):14983-90
  • Doh-Ura K, Iwaki T, Caughey B. Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation. J Virol 2000;74(10):4894-7
  • Kocisko DA, Come JH, Priola SA, et al. Cell-free formation of protease-resistant prion protein. Nature 1994;370(6489):471-4
  • Saborio GP, Permanne B, Soto C. Sensitive detection of pathological prion protein by cyclic amplification of protein misfolding. Nature 2001;411(6839):810-3
  • Castilla J, Saa P, Hetz C, Soto C. In vitro generation of infectious scrapie prions. Cell 2005;121(2):195-206
  • Race RE, Fadness LH, Chesebro B. Characterization of scrapie infection in mouse neuroblastoma cells. J Gen Virol 1987;68(Pt 5):1391-9
  • Nishida N, Harris DA, Vilette D, et al. Successful transmission of three mouse-adapted scrapie strains to murine neuroblastoma cell lines overexpressing wild-type mouse prion protein. J Virol 2000;74(1):320-5
  • Schatzl HM, Laszlo L, Holtzman DM, et al. A hypothalamic neuronal cell line persistently infected with scrapie prions exhibits apoptosis. J Virol 1997;71(11):8821-31
  • MRC Clinical Trials Unit. PRION-1: Randomised trial of quinacrine in human prion disease. Available at: URL:www.ctu.mrc.ac.uk/studies/cjd.asp [Accessed January 2008]
  • Kimberlin RH, Walker CA. The antiviral compound HPA-23 can prevent scrapie when administered at the time of infection. Arch Virol 1983;78(1-2):9-18
  • Dealler Stephen Francis (GB). GB2334211 (1999)
  • Sangaku Renkei Kiko Kyushu KK. JP2003040778; 2003
  • Gabizon R, Meiner Z, Halimi M, Ben-Sasson SA. Heparin-like molecules bind differentially to prion-proteins and change their intracellular metabolic fate. J Cell Physiol 1993;157(2):319-25
  • Caughey B, Raymond GJ. Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 1993;67(2):643-50
  • Caughey B, Brown K, Raymond GJ, Katzenstein GE, Thresher W. Binding of the protease-sensitive form of PrP (prion protein) to sulfated glycosaminoglycan and congo red [corrected]. J Virol 1994;68(4):2135-41
  • Adjou KT, Simoneau S, Sales N, et al. A novel generation of heparan sulfate mimetics for the treatment of prion diseases. J Gen Virol 2003;84(Pt 9):2595-603
  • Schonberger O, Horonchik L, Gabizon R, et al. Novel heparan mimetics potently inhibit the scrapie prion protein and its endocytosis. Biochem Biophys Res Commun 2003;312(2):473-9
  • Replicor, Inc. (CA). CA2538245 (2005)
  • Replicor, Inc. (CA); Juteau Jean-MARC (CA); Vaillant Andrew (CA). WO2006002540 (2006)
  • Replicor, Inc. (CA). US2007123480 (2007)
  • Kocisko DA, Vaillant A, Lee KS, et al. Potent antiscrapie activities of degenerate phosphorothioate oligonucleotides. Antimicrob Agents Chemother 2006;50(3):1034-44
  • Karpuj MV, Giles K, Gelibter-Niv S, et al. Phosphorothioate oligonucleotides reduce PrP levels and prion infectivity in cultured cells. Mol Med (Cambridge, Mass) 2007;13(3-4):190-8
  • Nat Inst of Asv Ind & Technol; Nat Veterinary Assay Lab Minis; Nat Agriculture & Food Res Org. JP2006320289 (2006)
  • Proske D, Gilch S, Wopfner F, et al. Prion-protein-specific aptamer reduces PrPSc formation. Chembiochem 2002;3(8):717-25
  • Rhie A, Kirby L, Sayer N, et al. Characterization of 2′-fluoro-RNA aptamers that bind preferentially to disease-associated conformations of prion protein and inhibit conversion. J Biol Chem 2003;278(41):39697-705
  • Shyng SL, Lehmann S, Moulder KL, Harris DA. Sulfated glycans stimulate endocytosis of the cellular isoform of the prion protein, PrPC, in cultured cells. J Biol Chem 1995;270(50):30221-9
  • Kimberlin RH, Walker CA. Suppression of scrapie infection in mice by heteropolyanion 23, dextran sulfate, and some other polyanions. Antimicrob Agents Chemother 1986;30(3):409-13
  • Ehlers B, Diringer H. Dextran sulphate 500 delays and prevents mouse scrapie by impairment of agent replication in spleen. J Gen Virol 1984;65(Pt 8):1325-30
  • Farquhar CF, Dickinson AG. Prolongation of scrapie incubation period by an injection of dextran sulphate 500 within the month before or after infection. J Gen Virol 1986;67(Pt 3):463-73
  • Ladogana A, Casaccia P, Ingrosso L, et al. Sulphate polyanions prolong the incubation period of scrapie-infected hamsters. J Gen Virol 1992;73(Pt 3):661-5
  • Doh-Ura K, Ishikawa K, Murakami-Kubo I, et al. Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. J Virol 2004;78(10):4999-5006
  • Supattapone S, Wille H, Uyechi L, et al. Branched polyamines cure prion-infected neuroblastoma cells. J Virol 2001;75(7):3453-61
  • Solassol J, Crozet C, Perrier V, et al. Cationic phosphorus-containing dendrimers reduce prion replication both in cell culture and in mice infected with scrapie. J Gen Virol 2004;85(Pt 6):1791-9
  • Winklhofer KF, Tatzelt J. Cationic lipopolyamines induce degradation of PrPSc in scrapie-infected mouse neuroblastoma cells. Biol Chem 2000;381(5-6):463-9
  • Yudovin-Farber I, Azzam T, Metzer E, Taraboulos A, Domb AJ. Cationic polysaccharides as antiprion agents J Med Chem 2005;48(5):1414-20
  • Supattapone S, Nguyen HO, Cohen FE, Prusiner SB, Scott MR. Elimination of prions by branched polyamines and implications for therapeutics. Proc Natl Acad Sci USA 1999;96(25):14529-34
  • US Health (US). WO9401116 (1994)
  • Caughey B, Race RE. Potent inhibition of scrapie-associated PrP accumulation by congo red. J Neurochem 1992;59(2):768-71
  • Demaimay R, Chesebro B, Caughey B. Inhibition of formation of protease-resistant prion protein by Trypan Blue, Sirius Red and other Congo Red analogs. Arch Virol Suppl 2000;(16):277-83
  • Ingrosso L, Ladogana A, Pocchiari M. Congo red prolongs the incubation period in scrapie-infected hamsters. J Virol 1995;69(1):506-8
  • Poli G, Martino PA, Villa S, et al. Evaluation of antiprion activity of congo red and its derivatives in experimentally infected hamsters. Arzneimittelforschung 2004;54(7):406-15
  • Gray LE Jr, Ostby JS. The effects of prenatal administration of azo dyes on testicular development in the mouse: a structure activity profile of dyes derived from benzidine, dimethylbenzidine, or dimethoxybenzidine. Fundam Appl Toxicol 1993;20(2):177-83
  • Rudyk H, Vasiljevic S, Hennion RM, et al. Screening Congo Red and its analogues for their ability to prevent the formation of PrP-res in scrapie-infected cells. J Gen Virol 2000;81(Pt 4):1155-64
  • Rudyk H, Knaggs MH, Vasiljevic S, et al. Synthesis and evaluation of analogues of Congo red as potential compounds against transmissible spongiform encephalopathies. Eur J Med Chem 2003;38(6):567-79
  • Demaimay R, Harper J, Gordon H, et al. Structural aspects of Congo red as an inhibitor of protease-resistant prion protein formation. J Neurochem 1998;71(6):2534-41
  • Caspi S, Halimi M, Yanai A, et al. The antiprion activity of Congo red. Putative mechanism. J Biol Chem 1998;273(6):3484-9
  • Ishikawa K, Kudo Y, Nishida N, et al. Styrylbenzoazole derivatives for imaging of prion plaques and treatment of transmissible spongiform encephalopathies. J Neurochem 2006;99(1):198-205
  • Kawasaki Y, Kawagoe K, Chen CJ, et al. Orally administered amyloidophilic compound is effective in prolonging the incubation periods of animals cerebrally infected with prion diseases in a prion strain-dependent manner. J Virol 2007;81(23):12889-98
  • Barbieri B, Giuliani FC, Bordoni T, et al. Chemical and biological characterization of 4′-iodo-4′-deoxydoxorubicin. Cancer Res 1987;47(15):4001-6
  • Tagliavini F, McArthur RA, Canciani B, et al. Effectiveness of anthracycline against experimental prion disease in Syrian hamsters. Science 1997;276(5315):1119-22
  • Forloni G, Iussich S, Awan T, et al. Tetracyclines affect prion infectivity. Proc Natl Acad Sci USA 2002;99(16):10849-54
  • Tagliavini F, Forloni G, Colombo L, et al. Tetracycline affects abnormal properties of synthetic PrP peptides and PrP(Sc) in vitro. J Mol Biol 2000;300(5):1309-22
  • Gilch S, Winklhofer KF, Groschup MH, et al. Intracellular re-routing of prion protein prevents propagation of PrP(Sc) and delays onset of prion disease. EMBO J 2001;20(15):3957-66
  • Nunziante M, Kehler C, Maas E, et al. Charged bipolar suramin derivatives induce aggregation of the prion protein at the cell surface and inhibit PrPSc replication. J Cell Sci 2005;118(Pt 21):4959-73
  • Priola SA, Caughey B, Caughey WS. Novel therapeutic uses for porphyrins and phthalocyanines in the transmissible spongiform encephalopathies. Curr Opin Microbiol 1999;2(5):563-6
  • Caughey WS, Raymond LD, Horiuchi M, Caughey B. Inhibition of protease-resistant prion protein formation by porphyrins and phthalocyanines. Proc Natl Acad Sci USA 1998;95(21):12117-22
  • US Health (US); Caughey Winslow S (US); Caughey Byron (US). WO0009111 (2000)
  • US Health (US). US6632808 (2003)
  • Priola SA, Raines A, Caughey WS. Porphyrin and phthalocyanine antiscrapie compounds. Science 2000;287(5457):1503-6
  • Priola SA, Raines A, Caughey W. Prophylactic and therapeutic effects of phthalocyanine tetrasulfonate in scrapie-infected mice. J Infect Dis 2003;188(5):699-705
  • Kocisko DA, Caughey WS, Race RE, et al. A porphyrin increases survival time of mice after intracerebral prion infection. Antimicrob Agents Chemother 2006;50(2):759-61
  • Caughey WS, Priola SA, Kocisko DA, et al. Cyclic tetrapyrrole sulfonation, metals, and oligomerization in antiprion activity. Antimicrob Agents Chemother 2007;51(11):3887-94
  • Adjou KT, Demaimay R, Deslys JP, et al. MS-8209, a water-soluble amphotericin B derivative, affects both scrapie agent replication and PrPres accumulation in Syrian hamster scrapie. J Gen Virol 1999;80(Pt 4):1079-85
  • Demaimay R, Race R, Chesebro B. Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons. J Virol 1999;73(4):3511-3
  • Amyx H, Salazar DC, Gajdusek DC, Gibbs CJ Jr. Chemotherapeutic trials in experimental slow virus diseases. Neurology 1984;34(Suppl 1):149
  • Demaimay R, Adjou KT, Beringue V, et al. Late treatment with polyene antibiotics can prolong the survival time of scrapie-infected animals. J Virol 1997;71(12):9685-9
  • Mange A, Nishida N, Milhavet O, et al. Amphotericin B inhibits the generation of the scrapie isoform of the prion protein in infected cultures. J Virol 2000;74(7):3135-40
  • Brajtburg J, Elberg S, Bolard J, et al. Interaction of plasma proteins and lipoproteins with amphotericin B. J Infect Dis 1984;149(6):986-97
  • Caughey B, Baron GS. Prions and their partners in crime. Nature 2006;443(7113):803-10
  • Saint-Julien L, Joly V, Seman M, Carbon C, Yeni P. Activity of MS-8209, a nonester amphotericin B derivative, in treatment of experimental systemic mycoses. Antimicrob Agents Chemother 1992;36(12):2722-8
  • Adjou KT, Demaimay R, Lasmezas C, et al. MS-8209, a new amphotericin B derivative, provides enhanced efficacy in delaying hamster scrapie. Antimicrob Agents Chemother 1995;39(12):2810-2
  • Pocchiari M, Casaccia P, Ladogana A. Amphotericin B: a novel class of antiscrapie drugs. J Infect Dis 1989;160(5):795-802
  • Marella M, Lehmann S, Grassi J, Chabry J. Filipin prevents pathological prion protein accumulation by reducing endocytosis and inducing cellular PrP release. J Biol Chem 2002;277(28):25457-64
  • Sviridov D, Nestel P, Watts G. Statins and metabolism of high density lipoprotein. Cardiovasc Hematol Agents Med Chem 2007;5(3):215-21
  • Glassberg H, Rader DJ. Management of lipids in the prevention of cardiovascular events. Ann Rev Med 2007; In Press
  • Mok SW, Thelen KM, Riemer C, et al. Simvastatin prolongs survival times in prion infections of the central nervous system. Biochem Biophys Res Commun 2006;348(2):697-702
  • Kempster S, Bate C, Williams A. Simvastatin treatment prolongs the survival of scrapie-infected mice. Neuroreport 2007;18(5):479-82
  • Univ California (US); Prusiner Stanley B (US); Korth Carsten (US); May Barnaby CH (US). WO02096431 (2002)
  • Touchsensor Tech LLC (US). US2005020582 (2005)
  • Barret A, Tagliavini F, Forloni G, et al. Evaluation of quinacrine treatment for prion diseases. J Virol 2003;77(15):8462-9
  • Korth C, May BC, Cohen FE, Prusiner SB. Acridine and phenothiazine derivatives as pharmacotherapeutics for prion disease. Proc Natl Acad Sci USA 2001;98(17):9836-41
  • Roikhel VM, Fokina GI, Pogodina VV. Influence of aminasine on experimental scrapie in mice. Acta Virol 1984;28(4):321-4
  • Univ California (US). US2004229898 (2004)
  • Univ California (US); Prusiner Stanley B (US); Korth Carsten (US); May Barnaby CH (US). WO2005027824 (2005)
  • May BC, Fafarman AT, Hong SB, et al. Potent inhibition of scrapie prion replication in cultured cells by bis-acridines. Proc Natl Acad Sci USA 2003;100(6):3416-21
  • Sangaku Renkei Kiko Kyushu KK. JP2004099553 (2004)
  • Murakami-Kubo I, Doh-Ura K, Ishikawa K, et al. Quinoline derivatives are therapeutic candidates for transmissible spongiform encephalopathies. J Virol 2004;78(3):1281-8
  • Kocisko DA, Caughey B. Mefloquine, an antimalaria drug with antiprion activity in vitro, lacks activity in vivo. J Virol 2006;80(2):1044-6
  • Ertmer A, Gilch S, Yun SW, et al. The tyrosine kinase inhibitor STI571 induces cellular clearance of PrPSc in prion-infected cells. J Biol Chem 2004;279(40):41918-27
  • Jabbour E, Cortes J, Giles F, Kantarjian H. Current perspectives on the treatment of patients with chronic myeloid leukemia: an individualized approach to treatment. Cancer J 2007;13(6):357-65
  • Petzer AL, Gunsilius E, Hayes M, et al. Low concentrations of STI571 in the cerebrospinal fluid: a case report. B J Haematol 2002;117(3):623-5
  • Yun SW, Ertmer A, Flechsig E, et al. The tyrosine kinase inhibitor imatinib mesylate delays prion neuroinvasion by inhibiting prion propagation in the periphery. J Neurovirol 2007;13(4):328-37
  • Bate C, Reid S, Williams A. Phospholipase A2 inhibitors or platelet-activating factor antagonists prevent prion replication. J Biol Chem 2004;279(35):36405-11
  • Farooqui AA, Ong WY, Horrocks LA. Inhibitors of brain phospholipase A2 activity: their neuropharmacological effects and therapeutic importance for the treatment of neurologic disorders. Pharmacol Rev 2006;58(3):591-620
  • Nordstrom EK, Luhr KM, Ibanez C, Kristensson K. Inhibitors of the mitogen-activated protein kinase kinase 1/2 signaling pathway clear prion-infected cells from PrPSc. J Neurosci 2005;25(37):8451-6
  • Bueler H, Aguzzi A, Sailer A, et al. Mice devoid of PrP are resistant to scrapie. Cell 1993;73(7):1339-47
  • Prusiner SB, Groth D, Serban A, et al. Ablation of the prion protein (PrP) gene in mice prevents scrapie and facilitates production of anti-PrP antibodies. Proc Natl Acad Sci USA 1993;90(22):10608-12
  • Sakaguchi S, Katamine S, Shigematsu K, et al. Accumulation of proteinase K-resistant prion protein (PrP) is restricted by the expression level of normal PrP in mice inoculated with a mouse-adapted strain of the Creutzfeldt-Jakob disease agent. J Virol 1995;69(12):7586-92
  • Manson JC, Clarke AR, McBride PA, McConnell I, Hope J. PrP gene dosage determines the timing but not the final intensity or distribution of lesions in scrapie pathology. Neurodegeneration 1994;3(4):331-40
  • Mallucci GR, White MD, Farmer M, et al. Targeting cellular prion protein reverses early cognitive deficits and neurophysiological dysfunction in prion-infected mice. Neuron 2007;53(3):325-35
  • Mallucci G, Dickinson A, Linehan J, et al. Depleting neuronal PrP in prion infection prevents disease and reverses spongiosis. Science 2003;302(5646):871-4
  • Alnylam Europ AG (DE). EP1550719 (2005)
  • Alnylam Europ AG (DE). JP2007031443 (2007)
  • Alnylam Europ AG (DE). EP1798285 (2007)
  • Japan Health Sciences Foundation (JP); Hohjoh Hirohiko (JP). WO2005078093 (2005)
  • Tilly G, Chapuis J, Vilette D, Laude H, Vilotte JL. Efficient and specific down-regulation of prion protein expression by RNAi. Biochem Biophys Res Commun 2003;305(3):548-51
  • Daude N, Marella M, Chabry J. Specific inhibition of pathological prion protein accumulation by small interfering RNAs. J Cell Sci 2003;116(Pt 13):2775-9
  • Pfeifer A, Eigenbrod S, Al-Khadra S, et al. Lentivector-mediated RNAi efficiently suppresses prion protein and prolongs survival of scrapie-infected mice. J Clin Invest 2006;116(12):3204-10
  • Collinge J, Whittington MA, Sidle KC, et al. Prion protein is necessary for normal synaptic function. Nature 1994;370(6487):295-7
  • Tobler I, Gaus SE, Deboer T, et al. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 1996;380(6575):639-42
  • Nishida N, Tremblay P, Sugimoto T, et al. A mouse prion protein transgene rescues mice deficient for the prion protein gene from purkinje cell degeneration and demyelination. Lab Invest 1999;79(6):689-97
  • McLennan NF, Brennan PM, McNeill A, et al. Prion protein accumulation and neuroprotection in hypoxic brain damage. Am J Pathol 2004;165(1):227-35
  • Sakurai-Yamashita Y, Sakaguchi S, Yoshikawa D, et al. Female-specific neuroprotection against transient brain ischemia observed in mice devoid of prion protein is abolished by ectopic expression of prion protein-like protein. Neuroscience 2005;136(1):281-7
  • Gauczynski S, Peyrin JM, Haik S, et al. The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J 2001;20(21):5863-75
  • Enari M, Flechsig E, Weissmann C. Scrapie prion protein accumulation by scrapie-infected neuroblastoma cells abrogated by exposure to a prion protein antibody. Proc Natl Acad Sci USA 2001;98(16):9295-9
  • Peretz D, Williamson RA, Kaneko K, et al. Antibodies inhibit prion propagation and clear cell cultures of prion infectivity. Nature 2001;412(6848):739-43
  • Donofrio G, Heppner FL, Polymenidou M, Musahl C, Aguzzi A. Paracrine inhibition of prion propagation by anti-PrP single-chain Fv miniantibodies. J Virol 2005;79(13):8330-8
  • Polymenidou M, Heppner FL, Pellicioli EC, et al. Humoral immune response to native eukaryotic prion protein correlates with antiprion protection. Proc Natl Acad Sci USA 2004;101(Suppl 2):14670-6
  • Korth C, Stierli B, Streit P, et al. Prion (PrPSc)-specific epitope defined by a monoclonal antibody. Nature 1997;390(6655):74-7
  • Medical Res Council (GB). US2006280745 (2006)
  • White AR, Enever P, Tayebi M, et al. Monoclonal antibodies inhibit prion replication and delay the development of prion disease. Nature 2003;422(6927):80-3
  • Perrier V, Solassol J, Crozet C, et al. Anti-PrP antibodies block PrPSc replication in prion-infected cell cultures by accelerating PrPC degradation. J Neurochem 2004;89(2):454-63
  • Miyamoto K, Nakamura N, Aosasa M, et al. Inhibition of prion propagation in scrapie-infected mouse neuroblastoma cell lines using mouse monoclonal antibodies against prion protein. Biochem Biophys Res Commun 2005;335(1):197-204
  • Kim CL, Karino A, Ishiguro N, et al. Cell-surface retention of PrPC by anti-PrP antibody prevents protease-resistant PrP formation. J Gen Virol 2004;85(Pt 11):3473-82
  • Stefan Weiss (DE/DE); Melvyn Little (GB/DE); Stefan Knackmuss (DE/DE); Clemence Rey (FR/DE); Peter Rottgen (DE/DE); Claudia Buttner (DE/DE); UWE Reusch (DE/DE). WO2005/035580 (2005)
  • Zuber C, Knackmuss S, Rey C, et al. Single chain Fv antibodies directed against the 37 kDa/67 kDa laminin receptor as therapeutic tools in prion diseases. Mol Immunol 2008;45(1):144-51
  • Meier P, Genoud N, Prinz M, et al. Soluble dimeric prion protein binds PrP(Sc) in vivo and antagonizes prion disease. Cell 2003;113(1):49-60
  • Univ Zuerich (CH). CA2518549 (2004)
  • Univ Zuerich (CH). EP1603951 (2005)
  • Waldmann TA. Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene 2007;26(25):3699-703
  • Stinchcombe TE, Socinski MA. Bevacizumab in the treatment of non-small-cell lung cancer. Oncogene 2007;26(25):3691-8
  • Kavanaugh A. Interleukin-6 inhibition and clinical efficacy in rheumatoid arthritis treatment–data from randomized clinical trials. Bull NYU Hosp Joint Dis 2007;65(Suppl 1):S16-20
  • Pescovitz MD. Rituximab, an anti-cd20 monoclonal antibody: history and mechanism of action. Am J Transplant 2006;6(5 Pt 1):859-66
  • Ludewigs H, Zuber C, Vana K, et al. Therapeutic approaches for prion disorders. Expert Rev Antiinfect Ther 2007;5(4):613-30
  • Sigurdsson EM, Brown DR, Daniels M, et al. Immunization delays the onset of prion disease in mice. Am J Pathol 2002;161(1):13-7
  • Ishibashi D, Yamanaka H, Yamaguchi N, et al. Immunization with recombinant bovine but not mouse prion protein delays the onset of disease in mice inoculated with a mouse-adapted prion. Vaccine 2007;25(6):985-92
  • Goni F, Knudsen E, Schreiber F, et al. Mucosal vaccination delays or prevents prion infection via an oral route. Neuroscience 2005;133(2):413-21
  • Szelenyi I, Nickel B, Borbe HO, Brune K. Mode of antinociceptive action of flupirtine in the rat. B J Pharmacol 1989;97(3):835-42
  • Dhar S, Bitting RL, Rylova SN, et al. Flupirtine blocks apoptosis in batten patient lymphoblasts and in human postmitotic CLN3- and CLN2-deficient neurons. Ann Neurol 2002;51(4):448-66
  • Perovic S, Schroder HC, Pergande G, Ushijima H, Muller WE. Effect of flupirtine on Bcl-2 and glutathione level in neuronal cells treated in vitro with the prion protein fragment (PrP106-126). Exp Neurol 1997;147(2):518-24
  • Forloni G, Angeretti N, Chiesa R, et al. Neurotoxicity of a prion protein fragment. Nature 1993;362(6420):543-6
  • Wong BS, Brown DR, Pan T, et al. Oxidative impairment in scrapie-infected mice is associated with brain metals perturbations and altered antioxidant activities. J Neurochem 2001;79(3):689-98
  • Choi SI, Ju WK, Choi EK, et al. Mitochondrial dysfunction induced by oxidative stress in the brains of hamsters infected with the 263 K scrapie agent. Acta Neuropathol (Berl) 1998;96(3):279-86
  • Milhavet O, McMahon HE, Rachidi W, et al. Prion infection impairs the cellular response to oxidative stress. Proc Natl Acad Sci USA 2000;97(25):13937-42
  • Guentchev M, Voigtlander T, Haberler C, Groschup MH, Budka H. Evidence for oxidative stress in experimental prion disease. Neurobiol Dis 2000;7(4):270-3
  • Guentchev M, Siedlak SL, Jarius C, et al. Oxidative damage to nucleic acids in human prion disease. Neurobiol Dis 2002;9(3):275-81
  • Drisko JA. The use of antioxidants in transmissible spongiform encephalopathies: a case report. J Am Coll Nutr 2002;21(1):22-5
  • Castilla J, Hetz C, Soto C. Molecular mechanisms of neurotoxicity of pathological prion protein. Curr Mol Med 2004;4(4):397-403
  • Hetz C, Russelakis-Carneiro M, Maundrell K, Castilla J, Soto C. Caspase-12 and endoplasmic reticulum stress mediate neurotoxicity of pathological prion protein. EMBO J 2003;22(20):5435-45
  • Lindholm D, Wootz H, Korhonen L. ER stress and neurodegenerative diseases. Cell Death Differ 2006;13(3):385-92
  • Paschen W. Endoplasmic reticulum: a primary target in various acute disorders and degenerative diseases of the brain. Cell Calcium 2003;34(4-5):365-83
  • Zhao L, Ackerman SL. Endoplasmic reticulum stress in health and disease. Curr Opin Cell Biol 2006;18(4):444-52
  • Kocisko DA, Baron GS, Rubenstein R, et al. New inhibitors of scrapie-associated prion protein formation in a library of 2000 drugs and natural products. J Virol 2003;77(19):10288-94
  • Kocisko DA, Morrey JD, Race RE, Chen J, Caughey B. Evaluation of new cell culture inhibitors of protease-resistant prion protein against scrapie infection in mice. J Gen Virol 2004;85(Pt 8):2479-83
  • Maxson L, Wong C, Herrmann LM, Caughey B, Baron GS. A solid-phase assay for identification of modulators of prion protein interactions. Anal Biochem 2003;323(1):54-64
  • Bach S, Talarek N, Andrieu T, et al. Isolation of drugs active against mammalian prions using a yeast-based screening assay. Nat Biotechnol 2003;21(9):1075-81
  • Ludwig Maximilians Uni Muenche (DE); Max Planck Gesellschaft (DE); Bertsch UWE (DE); Giese Armin (DE); Kretzschmar Hans (DE); Tavan Paul (DE); Hirschberger Thomas (DE); Bieschke Jan (US); Weber Petra (DE); Winklhofer Konstanze F (DE); Tatzelt Joerg (DE); Hartl F Ulrich (DE); Wuensch Gerda (DE); Hoegen Tobias Johannes (DE). WO2005116640 (2005)
  • Ludwig Maximilians Uni Muenche (DE); Max Planck Gesellschaft (DE). EP1751553 (2007)
  • Bertsch U, Winklhofer KF, Hirschberger T, et al. Systematic identification of antiprion drugs by high-throughput screening based on scanning for intensely fluorescent targets. J Virol 2005;79(12):7785-91
  • Kawatake S, Nishimura Y, Sakaguchi S, Iwaki T, Doh-Ura K. Surface plasmon resonance analysis for the screening of antiprion compounds. Biol Pharm Bull 2006;29(5):927-32
  • Kuwata K, Nishida N, Matsumoto T, et al. Hot spots in prion protein for pathogenic conversion. Proc Natl Acad Sci USA 2007;104(29):11921-6
  • Kuwata Kazuo; Nishida Noriyuki; Katamine Shigeru. JP2005120002 (2005)
  • Dohgu S, Yamauchi A, Takata F, et al. Uptake and efflux of quinacrine, a candidate for the treatment of prion diseases, at the blood–brain barrier. Cell Mol Neurobiol 2004;24(2):205-17
  • Univ Texas (US); Castilla Joaquin (US); SAA Paula (US); Soto Claudio (US). WO2006113915 (2006)
  • Univ Texas. US2006263767 (2006)
  • Saa P, Castilla J, Soto C. Presymptomatic detection of prions in blood. Science 2006;313(5783):92-4
  • Atarashi R, Moore RA, Sim VL, et al. Ultrasensitive detection of scrapie prion protein using seeded conversion of recombinant prion protein. Nat Methods 2007;4(8):645-50

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.