Advanced search
Publication Cover
Expert Opinion on Therapeutic Patents Volume 18, 2008 - Issue 10
Submit an article Journal homepage
88
Views
4
CrossRef citations to date
0
Altmetric
Review

Patented therapeutic RNAi strategies for neurodegenerative diseases of the CNS

Antonio Orlacchio Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, 64, Via del Fosso di Fiorano, 00143 Rome, Italy +39 06 501703308; +39 06 501703312; [email protected]; Università di Roma ‘Tor Vergata’, Dipartimento di Neuroscienze, Viale Oxford 81, 00133 Rome, Italy
,
Giorgio Bernardi Laboratorio di Neurogenetica, Centro Europeo di Ricerca sul Cervello (CERC), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia, 64, Via del Fosso di Fiorano, 00143 Rome, Italy +39 06 501703308; +39 06 501703312; [email protected]; Università di Roma ‘Tor Vergata’, Dipartimento di Neuroscienze, Viale Oxford 81, 00133 Rome, Italy
,
Aldo Orlacchio Università di Perugia, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Via del Giochetto, 06126 Perugia, Italy
&
Sabata Martino Università di Perugia, Dipartimento di Medicina Sperimentale e Scienze Biochimiche, Via del Giochetto, 06126 Perugia, Italy
Pages 1161-1174 | Published online: 09 Oct 2008

Bibliography

  • Patterson C, Feightner JW, Garcia A, et al. Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease. CMAJ 2008;178:548-56
  • Orlacchio A, Bernardi G, Orlacchio A, et al. RNA interference as a tool for Alzheimer's disease therapy. Mini Rev Med Chem 2007;7:1166-76
  • Costanzi E, Martino S, Persichetti E, et al. Effects of Vitamin C on Fibroblasts from Sporadic Alzheimer's Disease Patients. Neurochem Res 2007; Published online: 28 November 2007 doi: 10.1007/ s11064-007-9539-y
  • Rogaeva EA, Premkumar S, Grubber J, et al. An alpha-2-macroglobulin insertion-deletion polymorphism in Alzheimer disease. Nat Genet 1999;22:19-22
  • Freeman JW, Simmons M, Matos E. Parkinson disease: an incremental challenge. S D Med 2007;60:481-4
  • Balducci C, Pierguidi L, Persichetti E, et al. Lysosomal hydrolases in cerebrospinal fluid from subjects with Parkinson's disease. Mov Disord 2007;22:1481-4
  • Stamey W, Jankovic J. Impulse control disorders and pathological gambling in patients with Parkinson disease. Neurologist 2008;14:89-99
  • Kovacs GG, Budka H. Prion diseases: from protein to cell pathology. A J Pathol 2008;172:555-65
  • Tripathi VB, Al-Chalabi A. Molecular insights and therapeutic targets in amyotrophic lateral sclerosis. CNS Neurol Disord Drug Targets2008;7:11-9
  • Orlacchio A, Bernardi G, Orlacchio A, Martino S. Genetics of amyotrophic lateral sclerosis. Recent Res Dev Neurosci 2007;17-54
  • Orlacchio A, Kawarai T, Totaro A, et al. Hereditary spastic paraplegia: clinical genetic study of 15 families. Arch Neurol 2004;61:849-55
  • Orlacchio A, Kawarai T, Gaudiello F, et al. New locus for hereditary spastic paraplegia maps to chromosome 1p31.1-1p21.1. Ann Neurol 2005;58:423-9
  • Stack EC, Ferrante RJ. Huntington's disease: progress and potential in the field. Expert Opin Investig Drugs 2007;16:1933-53
  • Wild EI, Tabrizi SJ. Huntington's disease phenocopy syndromes. Curr Opin Neurol 2007;20:681-7
  • Martino S, Emiliani C, Tancini B, et al. Absence of metabolic cross-correction in Tay-Sachs cells: implication in gene therapy. J Biol Chem 2002;277:20177-94
  • Martino S, Cavalieri C, Emiliani C, et al. Restoration of GM2 ganglioside metabolism in bone marrow-derived stromal cells from Tay Sachs disease animal model. Neurochem Res 2002;27:793-800
  • Arfi A, Bourgoin C, Basso L, et al. Bicistronic lentiviral vector corrects beta-hexosaminidase deficiency in transduced and cross-corrected human Sandhoff fibroblasts. Neurobiol Disease 2005;20:583-93
  • Martino S, Marconi P, Tancini B , et al. A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease. Hum Mol Genet 2005;14:2113-23
  • Martino S, Orlacchio A. Cellule staminali e GM2 gangliosidosi. in “ISS Annali” 2005:27-8
  • Tosi G, Costantino L, Ruozi B, et al. Polymeric nanoparticles for the drug delivery to the central nervous system. Expert Opin Drug Deliv 2008;5:155-74
  • Jallouli Y, Paillard A, Chang J, et al. Influence of surface charge and inner composition of porous nanoparticles to cross blood-brain barrier in vitro. Int J Pharm 2007;344:103-9
  • Lo Bianco C, Schneider Bl, Bauer M, et al. Lentiviral vector delivery of parkin prevents dopaminergic degeneration in an alpha-synuclein rat model of Parkinson's disease. Proc Nat Acad Sci USA 2004;101:17510-15
  • Consiglio A, Quattrini A, Martino S, et al. In vivo gene therapy of metachromatic leukodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Nat Med 2001;7:310-6
  • Consiglio A, Martino S, Dolcetta D, et al. Metabolic correction in oligodendrocytes derived from metachromatic leukodystrophy mouse model by using encapsulated recombinant myoblasts. J Neurol Sci 2007;255:7-16
  • Ulusoy A, Bjorklund T, Hermening S, Kirik D. In vivo gene delivery for development of mammalian models for Parkinson's disease. Exp Neurol 2008;209:89-100
  • Federici T, Boulis N. Gene therapy for peripheral nervous system diseases. Curr Gene Ther 2007;7:239-48
  • Lundstrom K. Prospects of treating neurological diseases by gene therapy. Curr Opin Investig Drugs 2007;8:34-40
  • Cardone M. Prospects for gene therapy in inherited neurodegenerative diseases. Curr Opin Neurol 2007;20:151-8
  • Davidson BL, Breakefield XO. Viral vectors for gene delivery to the nervous system. Nat Rev Neurosci 2003;4:353-64
  • Biffi A, Capotondo A, Fasano S, et al. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J Clin Invest 2006;116:3070-82
  • Worgall S, Sondhi D, Hackett NR, et al. Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther 2008;19:463-74
  • Lindvall O, Kokaia Z. Stem cells for the treatment of neurological disorders. Nature 2006;441:1094-6
  • Picinich SC, Mishra PJ, Mishra P, et al. The therapeutic potential of mesenchymal stem cells. Cell- & tissue-based therapy. Expert Opin Biol Ther 2007;7:965-73
  • Imitola J, Khoury SJ. Neural stem cells and the future treatment of neurological diseases: raising the standard. Methods Mol Biol 2008;438:9-16
  • Muller F, Snyder EY, Loring JF. Gene therapy: can neural stem cells deliver? Nat Rev Neurosci 2006;7:75-84
  • Gage FH. Mammalian neural stem cells. Science 2000;287:1433-38
  • Bjorklund A, Lindvall O. Cell replacement therapies for central nervous system disorders. Nat Neurosci 2000;3:537-44
  • Kim M, Lee ST, Chu K, Kim SU. Stem cell-based cell therapy for Huntington disease: A review. Neuropathology 2008;28:1-9
  • Lee ST, Chu K, Park JE, et al. Intravenous administration of human neural stem cells induces functional recovery in Huntington's disease rat model. Neurosci Res 2005;52:243-9
  • Wang Y, Chen S, Yang D, Le WD. Stem cell transplantation: a promising therapy for Parkinson's disease. J Neuroimmune Pharmacol 2007;2:243-50
  • Goya RL, Kuan WL, Barker RA. The future of cell therapies in the treatment of Parkinson's disease. Expert Opin Biol Ther 2007;7:1487-98
  • Grimm D, Kay MA. Therapeutic application of RNAi: is mRNA targeting finally ready for prime time? J Clin Invest 2007;117:3633-41
  • Liu G, Wong-Staal F, Li QX. Development of new RNAi therapeutics. Histol Histopathol 2007;22:211-7
  • Davidson BL, Boudreau RL. RNA interference: a tool for querying nervous system function and an emerging therapy. Neuron 2007;53:781-8
  • Takeshita F, Ochiya T. Therapeutic potential of RNA interference against cancer. Cancer Sci 2006;97:689-96
  • Grünweller A, Hartmann RK. RNA interference as a gene-specific approach for molecular medicine. Curr Med Chem 2005;12:3143-61
  • Fire A, Xu S, Montgomery MK. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature 1998;391:806-11
  • Fire A. Genetic inhibition by double-stranded RNA. US6506559; 1998
  • Schmidt C. Negotiating the RNAi patent thicket. Nat Biotechnol 2007;25:273-5
  • Bartel DP. The uses of 21-23 sequence-specific mediators of double-stranded RNA interference as a tool to study gene function and as a gene-specific therapeutic US09821832; 2001
  • Tuschl T. RNA interference mediating small RNA molecules. US7056704; 2006
  • Tuschl T. RNA interference mediating small RNA molecules. US7078196; 2006
  • Liu X, Fortin K, Mourelatos Z. MicroRNAs: biogenesis and molecular functions. Brain Pathol 2008;18:113-21. Review
  • Lee Y, Jeon K, Lee JT. MicroRNAmaturation: stepwise processing and subcellular localization. EMBO J 2002;21:4663-70
  • Denli AM, Tops BB, Plasterk RH, et al. Processing of primary microRNAs by the Microprocessor complex. Nature 2004;432:231-5
  • Gregory RI, Yan KP, Amuthan G, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004;432:235-40
  • Han J, Lee Y, Yeom KH, Kim YK, et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev 2004;18:3016-27
  • Landthaler M, Yalcin A, Tuschl T. The human DiGeorge syndrome critical region gene 8 and its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol 2004;14:2162-7
  • Lee Y, Ahn C, Han J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003;425:415-9
  • Guil S, Caceres JF. The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a. Nat Struct Mol Biol 2007;14:591-6
  • Fukuda T, Yamagata K, Fujiyama S, et al. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol 2007;9:604-11
  • Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA 2004;10:185-91
  • Lund E, Guttinger S, Calado A, et al. Nuclear export of microRNA precursors. Science 2004;303:95-8
  • Yi R, Qin Y, Macara IG, Cullen BR. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev 2003;17:3011-6
  • Bernstein E, Kim SY, Carmell MA, et al. Dicer is essential for mouse development. Nat Gene 2003;35:215-7
  • Zhang H, Kolb FA, Jaskiewicz L, et al. Single processing center models for human Dicer and bacterial RNase III. Cell 2004;118:57-68
  • Sheth U, Parker R. Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 2003;300:805-8
  • Voinnet O. Non-cell autonomous RNA silencing. FEBS Lett 2005;579:5858-71
  • Kolb FA, Zhang H, Jaronczyk K, et al. Human dicer: purification, properties, and interaction with PAZ PIWI domain proteins. Methods Enzymol 2005;392:316-36
  • Macrae IJ, Zhou K, Li F, et al. Structural basis for double-stranded RNA processing by Dicer. Science 2006;311:195-8
  • Ma JB, Ye K, Patel DJ. Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature 2004;429:318-22
  • Findley SD, Tamanaha M, Clegg NJ, et al. Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage. Development 2003;130:859-71
  • Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature 2001;409:363-6
  • Filipowicz W. RNAi: the nuts and bolts of the RISC machine. Cell 2005;122:17-20
  • Quay SC. DICER substrate RNA peptide conjugates and methods for RNA therapeutics. WO2008022046; 2008
  • Agrawal N, Dasaradhi PV, Mohmmed A, et al. RNA interference: biology, mechanism, and applications. Microbiol Mol Biol Rev 2003;67:657-85
  • Aygun H. Novel tandem siRNAS. WO2007091269; 2005
  • Jaronczyk K, Carmichael JB, Hobman TC. Exploring the functions of RNA interference pathway proteins: some functions are more RISC than others? Biochem J 2005;387:561-71
  • Blaszczyk J, Tropea JE, Bubunenko M. Crystallographic and modeling studies of RNase III suggest a mechanism for double-stranded RNA cleavage. Structure 2001;9:1225-36
  • Hutvagner G. Small RNA asymmetry in RNAi: function in RISC assembly and gene regulation. FEBS Lett 2005;579:5850-7
  • Song JJ, Liu J, Tolia NH, et al. The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nat Struct Biol 2003;10:1026-32
  • Matranga C, Tomari Y, Shin C, et al. Passenger-strand cleavage facilitates assembly of siRNA into Ago2-containing RNAi enzyme complexes. Cell 2005;123:607-20
  • Tomari Y, Matranga C, Haley B, et al. A protein sensor for siRNA asymmetry. Science 2004;306:1377-80
  • Tomari Y, Du T, Haley B, et al. RISC assembly defects in the Drosophila RNAi mutant armitage. Cell 2004;16:831-41
  • Chekulaeva M, Ephrussi A. Drosophila development: RNA interference ab ovo. Curr Biol 2004;14:R428-30
  • Ikeda K, Satoh M, Pauley KM, et al. Detection of the argonaute protein Ago2 and microRNAs in the RNA induced silencing complex (RISC) using a monoclonal antibody. J Immunol Methods 2006;317:38-44
  • Sen GL, Blau HM. Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies. Nat Cell Biol 2005;7:633-6
  • Martinez J. SIRNA kinase and methods of use. WO2007138043; 2007
  • Joshua-Tor L. Methods and compositions related to Argonaute proteins WO2006015258; 2006
  • Theurkauf WE. Manipulation of RNA interference through modulation of Armitage activity WO2005060721; 2005
  • Tomari Y, Zamore PD. Perspective: machines for RNAi. Genes Dev 2005;19:517-29
  • Liu J, Rivas FV, Wohlschlegel J, et al. A role for the P-body component GW182 in microRNA function. Nat Cell Biol 2005;7:1261-6
  • Jackson AL, Bartz SR, Schelter J, et al. Expression profiling reveals off-target gene regulation by RNAi. Nat Biotechnol 2003;21:635-7
  • Fedorov Y, Anderson EM, Birmingham A, et al. Off-target effects by siRNA can induce toxic phenotype. RNA 2006;12:1188-96
  • Lin X, Ruan X, Anderson MG, et al. siRNA-mediated off-target gene silencing triggered by a 7 nt complementation. Nucleic Acids Res 2005;33:4527-35
  • Perkel M. Therapeutic RNAi: Delivering the Future? Life Science Technologies, Published online 2 November 2007 doi: 10.1126/science.opms.p0700019
  • Wolfrum C, Shi S, Jayaprakash KN, et al. Mechanisms and optimization of in vivo delivery of lipophilic siRNAs. Nat Biotechnol 2007;25:1145-9
  • Liu B. Exploring cell type-specific internalizing antibodies for targeted delivery of siRNA. Brief Funct Genomic Proteomic 2007;6:112-9
  • Chen Y. Efficient gene suppression using a transfer RNA promoter in herpes virus vectors to deliver small interference RNAs. WO2006076251; 2006
  • Schulte RW. System for inducible, local and reversible gene silencing using RNA interference. EP1447453; 2003
  • Lu X. Screening methods. CA2496635; 2004
  • Carman J. Polynucleotides encoding novel Guanylate binding proteins.WO2005003299; 2005
  • Linnemann T. Novel G-CSF polypeptides, polynucleotides, modulators thereof, and methods of use . WO2005121174; 2005
  • Buckner JC, Brown PD, O'neill BP, et al. Central nervous system tumors. Mayo Clin Proc 2007;82:1271-86
  • Hassani Z, Lemkine GF, Erbacher P, et al. Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels. J Gene Med 2005;7:198-207
  • Zhang Y, Boado RJ, Pardridge WM. In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats. J Gene Med 2003;5:1039-45
  • Fountaine TM, Wood MJ, Wade-Martins R. Delivering RNA interference to the mammalian brain. Curr Gene Ther 2005;5:399-410. Review
  • Towne C, Raoul C, Schneider BL, Aebischer P. Systemic AAV6 delivery mediating RNA interference against SOD1: neuromuscular transduction does not alter disease progression in fALS mice. Mol Ther 2008;16:1018-25
  • Kumar P, Wu H, Mcbride JL, et al. Transvascular delivery of small interfering RNA to the central nervous system. Nature 2007;448:39-43
  • Morrissey DV, Blanchard K, Shaw L, et al. Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication. Hepatology 2005;41:1349-56
  • Judge AD, Bola G, Lee AC, Maclachlan I. Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo. Mol Ther 2006;13:494-505
  • Kim DH, Behlke MA, Rose SD, et al. Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nat Biotechnol 2005;23:222-6
  • Jones AR, Shusta EV. Blood-brain barrier transport of therapeutics via receptor-mediation. Pharm Res 2007;24:1759-71
  • Schröder U, Sabel BA. Nanoparticles, a drug carrier system to pass the blood-brain barrier, permit central analgesic effects of i.v. dalargin injections. Brain Res 1996;710:121-4
  • Koziara JM, Lockman PR, Allen DD, Mumper RJ. The blood–brain barrier and brain drug delivery. J Nanosci Nanotechnol 2006;6:2712-35
  • Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 2001;70:1-20
  • Ambruosi A, Yamamoto H, Kreuter J. Body distribution of polysorbate-80 and doxorubicin-loaded [C-14]poly(butyl cyanoacrylate) nanoparticles after i.v. administration in rats. J Drug Target 2005;13:535-42
  • Gao K, Jiang X. Influence of particle size on transport of methotrexate across blood brain barrier by polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Int J Pharm 2006;310:213-9
  • De Boer AG, Gaillard PJ. Strategies to improve drug delivery across the blood-brain barrier. Clin Pharmacokinet 2007;46:553-76
  • Makimura H, Mizuno TM, Mastaitis JW, et al. Reducing hypothalamic AGRP by RNA interference increases metabolic rate and decreases body weight without influencing food intake. BMC Neurosci 2002;7;3:18
  • Farah MH. RNAi silencing in mouse models of neurodegenerative diseases. Curr Drug Deliv 2007;4:161-7
  • Kim DH, Rossi JJ. Strategies for silencing human disease using RNA interference. Nat Rev Genet 2007;8:173-84
  • Wong GT, Manfra D, Poulet FM, et al. Chronic treatment with the gamma-secretase inhibitor LY-411,575 inhibits beta-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 2004;279:12876-82
  • Hildebrand KR. System and method for delivering polynucleotides to the central nervous system. 20050048641; 2005
  • Kaemmerer WF. Treatment of neurodegenerative disease through intracranial delivery of SIRNA. 20040162255; 2004
  • Guarnieri M, Carson BS, Khan A, et al. Flexible versus rigid catheters for chronic administration of exogenous agents into central nervous system tissues. J Neurosci Methods 2005;144:147-52
  • Abeliovich A.Vector-mediated gene regulation in midbrain dopamine neurons. 20060153807; 2006
  • Sengupta S. Nanocell drug delivery system. US2005266067; 2005
  • Mitchell GS. SIRNA delivery into mammalian nerve cells. 20050234000; 2005
  • Yan Q-S, Feng M-J, Yan S-E. RNA interference-mediated inhibition of brain-derived neurotrophic factor expression increases cocaine's cytotoxicity in cultured cells. Neuroscience Lett 2007;414:165-9
  • Bilotti F. Retrograde transport of SIRNA and therapeutic uses to treat neurologic disorders. US20080039415; 2007
  • Ambron R. Neuronal pain pathway.US2006216339; 2006
  • Nakashima MN, Yamashita K, Kataoka Y, et al. Time course of nitric oxide synthase activity in neuronal, glial, and endothelial cells of rat striatum following focal cerebral ischemia. Cell Mol Neurobiol 1995;5:341-9
  • Sung YJ, Walters ET, Ambron RT. A neuronal isoform of protein kinase G couples mitogen-activated protein kinase nuclear import to axotomy-induced long-term hyperexcitability in Aplysia sensory neurons. J Neuroscience 2004;24:7583-95
  • Hermanussen M. NMDA receptor antagonists in the medical intervention of metabolic disorders. US2006094674; 2006
  • Podsypanina K, Lee RT, Politi C, et al. An inhibitor of mTor reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice. Proc Natl Acad Sci USA 2001;98:10320-5
  • Heiko K,Wohlbold L,Oetzel C, et al. Mechanisms of clinical resistance to small molecule tyrosine kinase inhibitors targeting oncogenic tyrosine kinases. Am J PharmacoGenomics 2005;5:101-2
  • Judith S, Sebolt-Leopold JM. Mechanisms of drug inhibition of signalling molecules. Nature 2006;441:457-62
  • Alvarez RL. Methods and apparatus for scanning a band of frequencies by NQR using an array of high temperature superconductor sensors US2005014680; 2005
  • Yu J-Y, Taylor J, Deruiter SL, et al. Simultaneous inhibition of GSK3α and GSK3β using hairpin siRNA expression vectors. Mol Ther 2003;7:228-36
  • Jere EM. Gamma secretase notch biomarkers, 20070072227; 2007
  • Searfoss GH, Jordan WH, Calligaro DO, et al. Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor. J Biol Chem 2003;278:46107-16
  • Milano J, Mckay J, Dagenais C, et al. Modulation of notch processing by gamma-secretase inhibitors causes intestinal goblet cell metaplasia and induction of genes known to specify gut secretory lineage differentiation. Toxicol Sci 2004;82:341-58
  • Garofalo AW. Patents targeting γ-secretase inhibition and modulation for the treatment of Alzheimer's disease: 2004-2008. Expert Opin Ther Patents 2008;18:693-703
  • Schoeb EB. SIRNA therapeutics evaluating RNAi to treat Huntington's disease. US2004208862; 2004
  • Iwai T. Apparatus for patients of erectile dysfunction. US2005203014; 2005
  • Ma G, Xiao Y, He L. Recent progress in the study of Hedgehog signaling. J Genet Genomics 2008;35:129-37
  • Paladini RD, Saleh J, Qian C, et al. Modulation of hair growth with small molecule agonists of the hedgehog signaling pathway. J Invest Dermatol 2005;125:638-46
  • Frank-Kamenetsky M, Zhang XM, Bottega S, et al. Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists. J Biol 2002;1:10-2
  • Haydon, PG. Methods for treating neurological and psychiatric conditions. WO2007002285; 2007
  • Raymond-Delpech V, Towers PR, Sattelle DB. Gene silencing of selected calcium-signalling molecules in a Drosophila cell line using double-stranded RNA interference. Cell Calcium 2004;35:131-9
  • Goedert M, Spillantini MG. A century of Alzheimer's disease. Science 2006;314:777-81
  • Ansbury PT, Lashuel HA. A century-old debate on protein aggregation and neurodegeneration enters the clinic. Nature 2006;443:774-9
  • Turner RS. Alzheimer's disease. Semin Neurol 2006;26:499-506
  • Ohyagi Y, Tabira T. Intracellular amyloid beta-protein and its associated molecules in the pathogenesis of Alzheimer's disease. Mini Rev Med Chem 2006;6:1075-80
  • Goldgaber D, Lerman MI, Mcbride OW, et al. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 1987;235:877-80
  • Tsai Li-H. SIRNA based methods for treating Alzheimer's disease. 20070185042; 2007
  • Tanzi RE. Methods for reducing amyloid beta levels. 20060172964; 2006
  • Rogelia B, Mitchella JC, Millera CJ, et al. The X11/Mint family of adaptor proteins. Brain Res Rev 2006;52:305-15
  • Park JH, Strittmatter SM. Nogo receptor interacts with brain APP and Abeta to reduce pathologic changes in Alzheimer's transgenic mice [review]. Curr Alzheimer Res 2007;4:568-70
  • Hsu R, Woodroffe A, Lai WS, et al. Nogo Receptor 1 (RTN4R) as a candidate gene schizophrenia: analysis using human and mouse genetic approaches. PLoS ONE 2007;2:1234-41
  • Mcswiggen J. RNA interference mediated inhibition of nogo and nogo receptor gene expression using short interfering nucleic acid (SINA) 20070185043; 2007
  • Mi S, Lee X, Shao Z, et al. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci 2004;7:221-8
  • Shao Z, Browning JL, Lee X, et al. TAJ/TROY, an orphan TNF receptor family member, binds Nogo-66 receptor 1 and regulates axonal regeneration. Neuron 2005;45:353-9
  • Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 2001;57:S11-26
  • Nussbaum RL, Polymeropoulos MH. Genetics of Parkinson's disease. Hum Mol Genet 1997;6:1687-91
  • Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the alpha-synuclein gene Identified in families with Parkinson's disease. Science 1997;276:2045-7
  • Miller VM, Xia H, Marrs GL, et al. Allele-specific silencing of dominant disease genes. Proc Natl Acad Sci USA 2003;100:7195-200
  • Gonzalez-Alegre P, Miller VM, Davidson BL, Paulson HL.Toward therapy for DYT1 dystonia: allele-specific silencing of mutant TorsinA. Ann Neurol 2003;53:781-7
  • Abeliovich A. Protecting cell therapy for neurological disorders including Parkinson's disease. 20060171935; 2006
  • McSwiggen J. RNA interference mediated treatment of Parkinson disease using short interfering nucleic acid (SINA). 20050137155; 2005
  • Park Y-K, Park S-M, Choi Y, et al. A siDesigner: exon-based siRNA design server considering alternative splicing. Nucl Ac Res 2008;362:97-103
  • Bohn MC. SIRNA-mediated gene silencing of synuclein. 20070172462; 2007
  • Stack EC, Ferrante RJ. Huntington's disease: progress and potential in the field. Expert Opin Investig Drugs 2007;16:1933-53
  • Nakamura K, Aminoff MJ. Huntington's disease: clinical characteristics, pathogenesis and therapies. Drugs Today Barc 2007;43:97-116
  • Mcbride JL, Boudreau RL, Harper SQ, et al. Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proc Natl Acad Sci USA 2008;105:5868-73
  • Cox DR. Parkinson's disease-related disease compositions and methods. 20070092889; 2007
  • Kaemmerer WF. Compositions, devices and methods for treatment of Huntington's disease through intracranial delivery of SIRNA. 20070167389; 2007
  • Davidson BL. RNA interference suppresion of neurodegenerative diseases and methods of use thereof. 20050042646; 2005
  • Benjamin D. Small interference RNA (SIRNA) molecules for modulating superoxide dismutase. 20060229268; 2006
  • Winkles JA. TWEAK as a therapeutic target for treating central nervous system diseases associated with cerebral edema and cell death.WO2006052926; 2006
  • Franich NR, Fitzsimons HL, Fong DM, et al. AAV Vector-mediated RNAi of Mutant Huntingtin Expression Is Neuroprotective in a Novel Genetic Rat Model of Huntington's Disease. Mol Ther 2008; doi:10.1038/mt.2008.50
  • Winkles JA. The TWEAK-Fn14 cytokine-receptor axis: discovery, biology and therapeutic targeting [review]. Nat Rev Drug Discov 2008;7:411-25
  • Ariz López De Castro U. Methods for the in vitro diagnosis and in vitro prognosis of demyelinating diseases, and for the development of drugs against demyelinating diseases. WO2005064341; 2003
  • Ibar J-P. Process for the control of flow properties of polymers. WO2005119203; 2005
  • Alroy I. Trans-Golgi Network-associated processes, methods and compositions related thereto. WO2004098492; 2004
  • Bowles DE. Vecteurs chimeriques. WO2006066066; 2006
  • Brenz V. System for inducible, local and reversible gene silencing using RNA interference.WO2004072300; 2004
  • McSwiggen J. RNA interference mediated inhibition of desmoglein gene expression using short interfering nucleic acid (SINA). US20060241075; 2005
  • Choi DS. Composition for treatment of prevention of endometrial cancer and method of preventing or treating endometrial cancer using the composition. US20060264396; 2005
  • Fitzgerald K. Transcription factor RNA interference reagents and methods of use thereof. US20060234973; 2006
  • Ishii K. RNA interference induction element and use thereof. WO2006123800; 2006
  • Wegmann U. Optical scattering disk, use thereof, and wave front measuring apparatus. WO2006125600; 2006
  • Davis M. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof. WO2006105361; 2006
  • Guerciolini R. RNA interference mediated inhibition of stromal cell-derived factor-1 (sdf-1) gene expression using short interfering nucleic acid (SINA). WO2006128141; 2006
  • Behr JP. Oligonucleotides for RNA interference and biological applications thereof. WO2006128739; 2006
  • Cibelli J. Use of RNA interference for the creation of lineage specific ES and other undifferentiated cells and production of differentiated cells in vitro by co-culture. US20060240556; 2006
  • McSwiggen J. RNA interference mediated treatment of Alzheimer's disease using short interfering nucleic acid (SINA) 20070161596; 2007
  • Jensen M. Novel method for down-regulation of amyloid. 20070041945; 2007
  • Benjamin D. SIRNA-mediated gene silencing with viral vectors. 20060009408; 2006

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:

Order Reprints Request Corporate Permissions

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:

Request Academic Permissions

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.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.