Abstract
Neurodegenerative diseases represent a substantial burden for society in terms of both patient suffering and socio-economic costs. For example, in Europe nearly 3 million persons suffer from stroke, over 3 5 million from dementia (with a higher proportion of women than men) and about 1 million from Parkinson’s disease (PD). Overall, diseases of the nervous system, includingeyediseases, account for approximately 25% of all health costs in the EU, which in money terms translates into hundreds of billions of Euros. With increasing life expectancy, this cost is likely to greatly increase, since the prevalence of dementia is 18% of the population between 80 and 85 years of age and 32% between 85 and 90. Similarly, PD affects more than 10% of the population after the age of 85. There is no cure for most of the neurodegenerative diseases, and the very few available treatments are unsatisfactory. The urgent need to develop therapies will rely on the unravelling of the pathophysiological mechanisms underlying these afflictions and on the development and use of post-genomics and cell/gene transfer technologies.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aronov S, Marx R, Ginzburg I (1999) Identification of 3’UTR region implicated in tau mRNA stabilization in neuronal cells. J Mol Neurosci 12:131–145.
Auricchio A, Kobinger G, Anand V, Hildinger M, O’Connor E, Maguire AM, Wilson JM, Bennett J (2001) Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model. Human Mol Genet 10; 3075–3081.
Baumgartner BJ, Shine HD (1997) Targeted transduction of CNS neurons with adenoviral vectors carrying neurotrophic factor genes confers neuroprotection that exceeds the transduced population. J Neurosci 17: 6504–6511.
Benabid AL, Benazzouz A, Hoffmann D, Limousin P, Krack P, Pollak P (1998) Long-term electrical inhibition of deep brain targets in movement disorders. Movement Disord 13: 119–125.
Bilang-Bleuel A, Revah F, Colin P, Locquet I, Robert JJ, Mallet J, Horellou P (1997) Intrastriatal injection of an adenoviral vector expressing glial-cell-line-derived neurotrophic factor prevents dopaminergic neuron degeneration and behavioral impairment in a rat model of Parkinson disease. Proc Natl Acad Sci USA 94: 8818–8823.
Bruijn LI, Becher MW, Lee MK., Anderson KL, Jenkins NA, Copeland NG, Sisodia, SS, Rothstein JD, Borchelt DR, Price DL, Cleveland DW (1997) ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing indusions. Neuron 18,; 327–338.
Choi-Lundberg DL, Lin Q, Chang YN, Chiang YL., Hay CM, Mohajeri H, Davidson BI, Bohn MC (1997) Dopaminergic neurons protected from degeneration by GDNF gene therapy. Science 275: 838–841.
Corti O, Horellou P, Colin P, Cattaneo E., Mallet J (1996) Intracerebral tetracycline-dependent regulation of gene expression in grafts of neural precursors. Neuroreport 7: 1655–1659.
Corti O., Sabate O, Horellou P, Colin P, Dumas S, Buchet D, Buc-Caron MH, Mallet J (1999a) A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors. Nature Biotechnol 17: 349–354.
Corti O, Sanchez-Capelo A, Colin P, Hanoun N, Hamon M, Mallet J (1999b). Long-term doxycydine-controlled expression of human tyrosine hydroxylase after direct adenovirus-mediated gene transfer to a rat model of Parkinson’s disease. Proc Natl Acad Sci USA 96: 12120–12125.
Dal Canto MC, Gurney,ME (1995) Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS). Brain Res 676,:25–40.
Deng HX, Hentati A, Tainer JA, Iqbal Z, Cayabyab A, Hung WY, Getzoff ED, Hu P, Herzfeldt, B., Roos, R. P., and et al. (1993). Amyotrophic lateral sclerosis and structural defects in Cu,Zn superoxide dismutase. Science2611047–51.
Fan DS, Ogawa M, Fujimoto KI, Ikeguchi K, Ogasawara Y, Urabe M, Nishizawa M, Nakano I, Yoshida M, Nagatsu I, Ichinose H, Nagatsu T, Kurtzman GJ, Ozawa K (1998) Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L- amino acid decarboxylase genes using two separate adeno-associated virus vectors. Human Gene Ther 9: 2527–2535.
Finiels F, Gimenez y Ribotta M, Barkats,M, Samolyk ML, Robert J, Privat A, Revah F, Mallet J (1995) Specific and efficient gene transfer strategy offers new potentialities for the treatment of motor neurone diseases. Neuroreport 6: 2473–2478.
Gimenez y Ribotta M, Revah F, Pradier L, Loquet I, Mallet, J, Privat A (1997) Prevention of motoneuron death by adenovirus-mediated neurotrophic factors. J Neurosci Res 48: 281–285.
Gossen M, Bujard H (1992) Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 89: 5547–5551.
Gossen M, Freundlieb S, Bender G, Muller G., Hillen W, Bujard H (1995) Transcriptional activation by tetracyclines in mammalian cells. Science 268: 1766–1769.
Gravel C, Gotz R, Lorrain A, Sendtner M (1997) Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Nature Med 3: 765–770.
Gurney ME (1994) Transgenic-mouse model of amyotrophic lateral sclerosis. New Engl J Med 331: 1721–1722.
Gutteridge JM, Halliwell B (2000) Free radicals and antioxidants in the year. A historical look to the future. Ann NY Acad Sci 899,:136–147.
Hauser RA, Freeman TB, Snow BJ, Nauert M, Gauger L, Kordower H, Olanow CW (1999) Long-term evaluation of bilateral fetal nigral transplantation in Parkinson disease. Arch Neurol 56: 179–187.
Horellou P, Vigne E, Castel MN, Barneoud, P, Colin, P, Perricaudet,M, Delaere P, Mallet J (1994) Direct intracerebral gene transfer of an adenoviral vector expressing tyrosine hydroxylase in a rat model of Parkinson’s disease. Neuroreport 6:49–53.
Kay MA, Glorioso IC, Naldini L (2001) Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nature Med 7: 33–40.
Kordower J.H, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor,MD, CarveyP, Ling, Z, Trono D, Hantraye P, Deglon N, Aebischer P (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson’s disease. Science 290: 767–773.
Krasnykh VN, Mikheeva GV, Douglas JT, Curiel DT (1996) Generation of recombinant adenovirus vectors with modified fibers for altering viral tropism. J Virol 70: 6839–6846.
Le Gal La Salle G, Robert JJ, Berrard S, Ridoux V, Stratford-Perricaudet LD, Perricaudet M, Mallet J (1993) An adenovirus vector for gene transfer into neurons and glia in the brain. Science 25+9: 988–990.
Limousin P, Krack P, Pollak P, Benazzouz A, Ardouin,C, Hoffmann D, Benabid A L (1998) Electrical stimulation of the subthalamic nucleus in advanced Parkinson’s disease. New Engl J Med 339: 1105–1111.
Lin LF, Doherty DH, Lile JD, Bektesh S, Collins F (1993). GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132.
Loeb JE, Cordier WS, Harris ME, Weitzman MD, Hope TJ (1999) Enhanced expression of transgenes from adeno-associated virus vectors with the woodchuck hepatitis virus posttranscriptional regulatory element: implications for gene therapy. Human Gene Ther 10,: 2295–2305.
Millecamps S, Kiefer H, Navarro V, Geoffroy MC, Robert JJ, Finiels F, Mallet J, Barkats M (1999) Neuron-restrictive silencer elements mediate neuron specificity of adenoviral gene expression. Nature Biotechnol 17: 865–869.
Millecamps S, Nicolle D, Ceballos-Picot I, Mallet, J, Barkats M (2001) Synaptic sprouting increases the uptake capacities of motoneurons in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci USA 98: 7582–7587.
Millecamps S, Mallet J, Barkats M (2002) Adenoviral retrograde gene transfer in motoneurons is greatly enhanced by prior intramuscular inoculation with botulinum toxin. Human Gene Ther 13: 225–232.
Mitani K, Graham FL, Caskey CT, Kochanek S (1995) Rescue, propagation, and partial purification of a helper virus-dependent adenovirus vector. Proc Natl Acad Sci USA 92: 3854–3858.
Morelli AE, Larregina AT, Smith-Arica J, Dewey RA, Southgate,TD, Ambar B, Fontana A, Castro MG, Lowenstein PR (1999) Neuronal and glial cell type-specific promoters within adenovirus recombinants restrict the expression of the apoptosis-inducing molecule Fas ligand to predetermined brain cell types, and abolish peripheral liver toxicity. J Gen Virol 80: 571–583.
Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, TronoD (1996) In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science 272: 263–267.
Navarro V, Millecamps S, GeoffroyMC, Robert JJ. Valin A, Mallet J, Gal La Salle G.L (1999) Efficient gene transfer and long-term expression in neurons using a recombinant adenovirus with a neuron-specific promoter. Gene Ther 6: 1884–1892.
Palmer T D, Rosman GJ, Osborne WR, Miller AD (1991) Genetically modified skin fibroblasts persist long after transplantation but gradually inactivate introduced genes. Proc Natl Acad Sci USA 88: 1330–1334.
Paulding WR, Czyzyk-Krzeska MF (1999) Regulation of tyrosine hydroxylase mRNA stability by protein-binding, pyrimidine-rich sequence in the 3’-untranslated region. J Biol Chem 274: 2532–2538.
Poewe WH, Wenning GK (1996) The natural history of Parkinson’s disease. Neurology 47:S146–152.
Ripps ME. Huntley G.W, Hof PR, Morrison J, Gordon JW (1995) Transgenic mice expressing an altered murine superoxide dismutase gene provide an animal model of amyotrophic lateral sclerosis. Proc Natl Acad Sci USA 92: 689–693.
Rogers JT, Leiter LM, McPhee J, Cahill CM, Zhan SS, Potter H, Nilsson LN (1999) Translation of the alzheimer amyloid precursor protein mRNA is up-regulated by interleukin-1 through 5’-untranslated region sequences. J Biol Chem 274: 6421–6431.
Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX, Rahmani Z, Krizus A, McKenna-Yasek D, Cayabyab SM, Berger R, Tanzi RE, Halperin J, Herzfeldt B, Van den Bergh R, Hung W-Y Hung, Bird T, Deng G, Mulder DW, Smyth C, Laing NG, Soriano E, Pericak-Vance MA, Haines J, Rouleau GA, Gusella JS, Horvitz HR, Brown Jr RH (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362, 59–62.
Sauer H, Rosenblad C, Bjorklund A (1995) Glial cell line-derived neurotrophic factor but not transforming growth factor beta 3 prevents delayed degeneration of nigral dopaminergic neurons following striatal 6-hydroxydopamine lesion. Proc Natl Acad Sci USA 92: 8935–8939.
Tu PH, Raju P, Robinson KA, Gurney ME, Trojanowski JQ, Lee VM (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology resembling human amyotrophic lateral sclerosis lesions. Proc Natl Acad Sci USA 93,: 3155–3160.
Warita H, Itoyama, Y, Abe K (1999) Selective impairment of fast anterograde axonal transport in the peripheral nerves of asymptomatic transgenic mice with a G93A mutant SOD1 gene. Brain Res 819:120–131.
Wickham TJ, Tzeng E, Shears LL 2nd, Roelvink PW, Li Y, Lee GM, Brough DE, Lizonova A, Kovesdi I (1997) Increased in vitro and in vivo gene transfer by adenovirus vectors containing chimeric fiber proteins. J Virol 71: 8221–8229.
Williamson TL, Cleveland DW (1999) Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nature Neurosci 2: 50–56.
Wong PC, Pardo CA, Borchelt DR, Lee MK, Copeland NG, Jenkins NA, Sisodia, SS, Cleveland DW, Price DL (1995). An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14: 1105–1116.
Wong, PC, Borchelt, D.R, Lee M.K, Pardo CA, Thinakaran G, Martin LJ, Sisodia S S, Price DL (1998) Familial amyotrophic lateral sclerosis and Alzheimer’s disease. Transgenic models. Adv Exp Med Biol 446,:145–159.
Wood MJ, Charlton HM, Wood K J, Kajiwara K, Byrnes AP (1996) Immune responses to adenovirus vectors in the nervous system. Trends Neurosci 19:497–501.
Yang Y, Nunes F.A, Berencsi K, Furth EE, Gonczol E, Wilson JM (1994) Cellular immunity to viral antigens limits El-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91: 4407–4411.
Zennou V, Petit C, Guetard D, Nerhbass U, Montagnier L, Charneau,P (2000). HIV-1 genome nuclear import is mediated by a central DNA flap. Cell 101: 173–185.
Zennou V, Serguera C, Sarkis, C, Colin P, Perret E, Mallet J, Chameau P (2001) The HIV-1 DNA flap stimulates HIV vector-mediated cell transduction in the brain. Nature Biotechnol 19,:446–450.
Zhang B, Tu P, Abtahian F, Trojanowski JQ, Lee VM (1997) Neurofilaments and orthograde transport are reduced in ventral root axons of transgenic mice that express human SOD1 with a G93A mutation. J Cell Biol 139:1307–1315.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Barkats, M., Bemelmans, A., Brun, S., Corti, O., Sarkis, C., Mallet, J. (2003). Gene Therapy in the Central Nervous System. In: Mallet, J., Christen, Y. (eds) Neurosciences at the Postgenomic Era. Research and Perspectives in Neurosciences. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55543-5_11
Download citation
DOI: https://doi.org/10.1007/978-3-642-55543-5_11
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-62430-8
Online ISBN: 978-3-642-55543-5
eBook Packages: Springer Book Archive