PR Lowenstein, Gene Therapeutics Research Institute, Cedars‐Sinai Medical Center and Department of Medicine, David Geffer School of Medicine, University of California, Los Angeles, California, USA
MG Castro, Gene Therapeutics Research Institute, Cedars‐Sinai Medical Center and Department of Medicine, David Geffer School of Medicine, University of California, Los Angeles, California, USA
Published online: January 2006
DOI: 10.1038/npg.els.0005757
Gene therapy is the use of nucleic acids as drugs. This type of genetic pharmacology can be used to treat either inherited (e.g. Huntington disease) or mainly sporadic (e.g. Parkinson disease) neurological diseases.
Keywords: viral vectors; neurodegeneration; brain tumors; clinical trials in neurology; growth factors
| References | |
| Aebischer P, Schluep M, Deglon N, et al. (1996) Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients. Nature Medicine 2: 696–699. | |
| Bachoud-Levi AC, Deglon N, Nguyen JP, et al. (2000) Neuroprotective gene therapy for Huntington disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF. Human Gene Therapy 11: 1723–1729. | |
| Bankiewicz KS, Eberling JL, Kohutnicka M, et al. (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Experimental Neurology 164: 2–14. | |
| Benedetti S, Pirola B, Pollo B, et al. (2000) Gene therapy of experimental brain tumors using neural progenitor cells. Nature Medicine 6: 447–450. | |
| Blesch A, Grill RJ and Tuszynski MH (1998) Neurotrophin gene therapy in CNS models of trauma and degeneration. Progress in Brain Research 117: 473–484. | |
| Bohn MC (2000) Parkinson's disease: neurodegenerative disease particularly amenable to gene therapy. Molecular Therapy 1: 494–496. | |
| Bosch A, Perret E, Desmaris N and Heard JM (2000) Long term and significant correction of brain lesions in adult mucopolysaccharidosis type VII mice using recombinant AAV vectors. Molecular Therapy 1: 63–70. | |
| Brooks AI, Stein CS, Hughes SM, et al. (2002) Functional correction of established central nervous system deficits in an animal model of lysosomal storage disease with feline immunodeficiency virus-based vectors. Proceedings of the National Academy of Sciences of the United States of America 99: 6216–6221. | |
| Consiglio A, Quattrini A, Martino S, et al. (2001) In vivo gene therapy of metachromatic leudodystrophy by lentiviral vectors: correction of neuropathology and protection against learning impairments in affected mice. Nature Medicine 7: 310–316. | |
| Constantini LC, Bakowska JC, Breakefield XO and Isaacson O (2000) Gene therapy in the CNS. Gene Therapy 7: 93–109. | |
| Davidson BL, Stein CS, Heth JA, et al. (2000) Recombinant adeno-associated virus type 2, 4 and 5 vectors: transduction of a variant cell types and regions in the mammalian central nervous system. Proceedings of the National Academy of Sciences of the United States of America 97: 3428–3432. | |
| Dewey RA, Morrissey G, Cowsill CM, et al. (1999) Chronic brain inflammation and persistent herpes simplex virus 1 thymidine kinase expression in survivors of syngeneic glioma treated by adenovirus-mediated gene therapy: implications for clinical trials. Nature Medicine 5: 1256–1263. | |
| Gerdes C, Castro MG and Lowenstein PR (2000) Strong promoters are the key to highly efficient, noninflammatory and noncytotoxic adenoviral-mediated transgene delivery into the brain in vivo. Molecular Therapy 2: 330–338. | |
| Glorioso JC and Fink DJ (2002) Use of HSV vectors to modify the nervous system. Current Opinion in Drug Discovery Development 5(2): 289–295. | |
| Kirik D, Rosenblad C, Bjorklund A and Mandel RJ (2000) Long-term rAAV-mediated gene transfer of GDNF in the rat Parkinson' model: intrastriatal but not intranigral transduction promotes functional regeneration in the lesioned nigrostriatal system. Journal of Neuroscience 20: 4686–4700. | |
| Kordower JH, Emborg ME, Bloch J, et al. (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson disease. Science 290: 767–773. | |
| Markert JM, Medlock MD, Rabkin SD, et al. (2000) Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: results of a phase 1 trial. Gene Therapy 7: 867–874. | |
| Mattson MP, Chan SL and Duan W (2002) Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiological Reviews 82: 637–672. | |
| Rainov NG on behalf of the GLI 328 International Study Group (2000) A phase III clinical evaluation of herpes simplex virus type 1 thymidine kinase and ganciclovir gene therapy as an adjuvant to surgical resection and radiation in adults with previously untreated glioblastoma multiforme. Human Gene Therapy 11: 2389–2401. | |
| Rampling R, Cruickshank G, Papanastassiou V, et al. (2000) Toxicity evaluation of replication-competent herpes simplex virus (ICP34.5 n mutant 1716) in patients with recurrent malignant glioma. Gene Therapy 7: 859–866. | |
| Russell SJ and Cosset FL (1999) Modifying the host range properties of retroviral vectors. Journal of Gene Medicine 1: 300–311. | |
| Sandmair AM, Loimas S, Puranen P, et al. (2000) Thymidine kinase gene therapy for human malignant glioma, using replication-deficient retroviruses or adenoviruses. Human Gene Therapy 11: 2197–2205. | |
| Smith-Arica J, Morelli AM, Larregina AT, et al. (2000) Cell type specific and regulatable transgenesis in the adult brain: adenovirus-encoded combined transcriptional targeting and inducible transgene expression. Molecular Therapy 2: 579–587. | |
| Thomas CE, Schiedner G, Kochanek S, Castro MG and Lowenstein PR (2000) Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: towards realistic long-term neurological gene therapy for chronic diseases. Proceedings of the National Academy of Sciences of the United States of America 97: 7482–7487. | |
| Wickham TJ (2000) Targeting adenovirus. Gene Therapy 7: 110–114. | |
| Yamada M, Oligino T, Mata M, et al. (1999) Herpes simplex virus vector-mediated expression of Bcl-2 prevents 6-hydroxydopamine-induced degeneration of neurons in the substantia nigra in vivo. Proceedings of the National Academy of Sciences of the United States of America 96: 4078–4083. | |
| Zermansky AJ, Bolognani F, Stone D, et al. (2001) Towards global and long-term neurological gene therapy: unexpected transgene dependent, high-level, and widespread distribution of HSV-1 thymidine kinase throughout the CNS. Molecular Therapy 4: 490–498. | |
| Further Reading | |
| book Chiocca EA and Breakefield XO (eds.) (1998) Gene Therapy for Neurological Disorders and Brain Tumors. Totowa, NJ: Humana Press. | |
| book Friedmann T (ed.) (1999) The Development of Human Gene Therapy. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press. | |
| Lowenstein PR (2002) Immunology of viral-vector mediated gene transfer into the brain: an evolutionary and developmental perspective. Trends in Immunology 23: 23–30. | |
| book Lowenstein PR (ed.) (2003) "Special Issue: Immune responses to viral vextors". Gene Therapy (in press). | |
| Lowenstein PR and Castro MG (2002) Progress and challenges in viral vector-mediated gene transfer to the brain. Current Opinion in Molecular Therapy 4: 359–371. | |
| Lysaght MJ and Aebischer P (1999) Encapsulated cells as therapy. Scientific American 280: 76–82. | |
Copyright © 2000-2013 by John Wiley & Sons, Inc., or related companies. All rights reserved.
