Alexander J Smith

Summary

Affiliation: University College London
Country: UK

Publications

  1. doi request reprint Gene supplementation therapy for recessive forms of inherited retinal dystrophies
    A J Smith
    Department of Genetics, UCL Institute of Ophthalmology, London, UK
    Gene Ther 19:154-61. 2012
  2. ncbi request reprint AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa
    Alexander J Smith
    Molecular Genetics, Institute of Ophthalmology, London, United Kingdom
    Mol Ther 8:188-95. 2003
  3. doi request reprint Prospects for retinal gene replacement therapy
    Alexander J Smith
    University College London Institute of Ophthalmology, Department of Genetics, 11 43 Bath Street, London EC1 V 9EL, UK
    Trends Genet 25:156-65. 2009
  4. ncbi request reprint In contrast to AAV-mediated Cntf expression, AAV-mediated Gdnf expression enhances gene replacement therapy in rodent models of retinal degeneration
    Prateek K Buch
    Division of Molecular Therapy, Institute of Ophthalmology, University College London, 11 43 Bath Street, London EC1V 9EL, UK
    Mol Ther 14:700-9. 2006
  5. pmc Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice
    Susie E Barker
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, UK
    J Gene Med 11:486-97. 2009
  6. pmc Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy
    Freya M Mowat
    Department of Genetics, University College London Institute of Ophthalmology, London, United Kingdom
    Am J Pathol 180:1726-39. 2012
  7. pmc Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development
    Clemens A K Lange
    Department of Genetics, Institute of Ophthalmology, NIHR Biomedical Research Centre for Ophthalmology, University College London, London EC1V 9EL, UK
    Development 139:2340-50. 2012
  8. pmc Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy
    Livia S Carvalho
    The Department of Genetics, UCL Institute of Ophthalmology, London, UK
    Hum Mol Genet 20:3161-75. 2011
  9. ncbi request reprint Long-term evaluation of retinal function in Prph2Rd2/Rd2 mice following AAV-mediated gene replacement therapy
    Frank C Schlichtenbrede
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK
    J Gene Med 5:757-64. 2003
  10. pmc Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of leber congenital amaurosis caused by guanylate cyclase-1 deficiency
    Marija Mihelec
    Department of Genetics, University College London, Institute of Ophthalmology, London, United Kingdom
    Hum Gene Ther 22:1179-90. 2011

Collaborators

Detail Information

Publications25

  1. doi request reprint Gene supplementation therapy for recessive forms of inherited retinal dystrophies
    A J Smith
    Department of Genetics, UCL Institute of Ophthalmology, London, UK
    Gene Ther 19:154-61. 2012
    ..Here, we examine the progress of gene supplementation therapy in the retina, and discuss the potential for using gene therapy to treat different forms of inherited retinal degeneration...
  2. ncbi request reprint AAV-Mediated gene transfer slows photoreceptor loss in the RCS rat model of retinitis pigmentosa
    Alexander J Smith
    Molecular Genetics, Institute of Ophthalmology, London, United Kingdom
    Mol Ther 8:188-95. 2003
    ..5-fold higher in treated than in control eyes. This study provides strong support for the development of AAV-mediated gene therapy for RP caused by mutations in the MERTK gene...
  3. doi request reprint Prospects for retinal gene replacement therapy
    Alexander J Smith
    University College London Institute of Ophthalmology, Department of Genetics, 11 43 Bath Street, London EC1 V 9EL, UK
    Trends Genet 25:156-65. 2009
    ..Here, we discuss the potential for treating other forms of retinal degeneration by gene therapy, focusing on the gene defects that are likely to be the most amenable to treatment...
  4. ncbi request reprint In contrast to AAV-mediated Cntf expression, AAV-mediated Gdnf expression enhances gene replacement therapy in rodent models of retinal degeneration
    Prateek K Buch
    Division of Molecular Therapy, Institute of Ophthalmology, University College London, 11 43 Bath Street, London EC1V 9EL, UK
    Mol Ther 14:700-9. 2006
    ..These data show for the first time that a combination of these approaches can provide enhanced rescue over gene replacement or growth factor therapy alone...
  5. pmc Subretinal delivery of adeno-associated virus serotype 2 results in minimal immune responses that allow repeat vector administration in immunocompetent mice
    Susie E Barker
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, UK
    J Gene Med 11:486-97. 2009
    ..However, one potential barrier to efficacious long-term therapy is the development of immune responses against the vector or transgene product...
  6. pmc Endogenous erythropoietin protects neuroretinal function in ischemic retinopathy
    Freya M Mowat
    Department of Genetics, University College London Institute of Ophthalmology, London, United Kingdom
    Am J Pathol 180:1726-39. 2012
    ..Endogenous EPO can protect neuroretinal function in ischemic retinopathy...
  7. pmc Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development
    Clemens A K Lange
    Department of Genetics, Institute of Ophthalmology, NIHR Biomedical Research Centre for Ophthalmology, University College London, London EC1V 9EL, UK
    Development 139:2340-50. 2012
    ....
  8. pmc Long-term and age-dependent restoration of visual function in a mouse model of CNGB3-associated achromatopsia following gene therapy
    Livia S Carvalho
    The Department of Genetics, UCL Institute of Ophthalmology, London, UK
    Hum Mol Genet 20:3161-75. 2011
    ..This study represents achievement of the most substantial restoration of visual function reported to date in an animal model of achromatopsia using a human gene construct, which has the potential to be utilized in clinical trials...
  9. ncbi request reprint Long-term evaluation of retinal function in Prph2Rd2/Rd2 mice following AAV-mediated gene replacement therapy
    Frank C Schlichtenbrede
    Department of Molecular Genetics, Institute of Ophthalmology, University College London, UK
    J Gene Med 5:757-64. 2003
    ..Here we quantify the functional rescue over a 15-week time course and present a detailed analysis of the improvement in retinal function...
  10. pmc Long-term preservation of cones and improvement in visual function following gene therapy in a mouse model of leber congenital amaurosis caused by guanylate cyclase-1 deficiency
    Marija Mihelec
    Department of Genetics, University College London, Institute of Ophthalmology, London, United Kingdom
    Hum Gene Ther 22:1179-90. 2011
    ..To date, this is the most effective rescue of the Gucy2e(-/-) mouse model of LCA and we propose that a vector, similar to the one used in this study, could be suitable for use in a clinical trial of gene therapy for LCA1...
  11. doi request reprint Effect of gene therapy on visual function in Leber's congenital amaurosis
    James W B Bainbridge
    Institute of Ophthalmology, University College London, London, United Kingdom
    N Engl J Med 358:2231-9. 2008
    ..These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747 [ClinicalTrials.gov].)...
  12. pmc Long-term survival of photoreceptors transplanted into the adult murine neural retina requires immune modulation
    Emma L West
    Department of Genetics, University College London Institute of Ophthalmology, London, United Kingdom
    Stem Cells 28:1997-2007. 2010
    ..These findings suggest that autologous donor cells are optimal for therapeutic approaches to repair the neural retina, though with immune suppression nonautologous donors may be effective...
  13. ncbi request reprint Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis
    Cathryn A Broderick
    Division of Molecular Therapy, Institute of Ophthalmology, University College, London, 11 43 Bath Street, London EC1V 9EL, UK
    Mol Ther 12:369-73. 2005
    ....
  14. doi request reprint Adult ciliary epithelial cells, previously identified as retinal stem cells with potential for retinal repair, fail to differentiate into new rod photoreceptors
    Sara Gualdoni
    Developmental Biology Unit, Institute of Child Health, University College London, London, UK
    Stem Cells 28:1048-59. 2010
    ..Therefore, we conclude that CE cells lack potential for photoreceptor differentiation and would require reprogramming to be useful as a source of new photoreceptors...
  15. pmc Gene therapy for retinitis pigmentosa and Leber congenital amaurosis caused by defects in AIPL1: effective rescue of mouse models of partial and complete Aipl1 deficiency using AAV2/2 and AAV2/8 vectors
    Mei Hong Tan
    Institute of Ophthalmology, NIHR Biomedical Research Centre, University College London, London, UK
    Hum Mol Genet 18:2099-114. 2009
    ..This is the first gene replacement study to report long-term rescue of a photoreceptor-specific defect and to demonstrate effective rescue of a rapid photoreceptor degeneration...
  16. ncbi request reprint CNTF gene transfer protects ganglion cells in rat retinae undergoing focal injury and branch vessel occlusion
    Robert E MacLaren
    Division of Molecular Therapy, Institute of Ophthalmology, University College London, London EC1V 9EL, UK
    Exp Eye Res 83:1118-27. 2006
    ..This approach may be relevant to optic nerve trauma and a variety of retinal vascular diseases that lead to swelling of the optic nerve head, provided CNTF can be delivered in a way that does not significantly suppress retinal function...
  17. doi request reprint Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina
    Anai Gonzalez-Cordero
    1 Department of Genetics, UCL Institute of Ophthalmology, London, UK 2
    Nat Biotechnol 31:741-7. 2013
    ..This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation. ..
  18. pmc Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy
    Mei Hong Tan
    Department of Genetics, Institute of Ophthalmology, University College London, London, United Kingdom
    PLoS ONE 7:e32330. 2012
    ..This data suggests that there are patients who have a reasonable window of opportunity for gene therapy in childhood...
  19. pmc HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia
    Freya M Mowat
    Department of Genetics, University College London Institute of Ophthalmology, London, United Kingdom
    PLoS ONE 5:e11103. 2010
    ....
  20. ncbi request reprint Comparative analysis of progenitor cells isolated from the iris, pars plana, and ciliary body of the adult porcine eye
    Angus Macneil
    Division of Molecular Therapy, Institute of Ophthalmology, University College London, 11 43 Bath Street, London, EC1V 9EL UK
    Stem Cells 25:2430-8. 2007
    ..Disclosure of potential conflicts of interest is found at the end of this article...
  21. ncbi request reprint Gene therapeutic prospects in early onset of severe retinal dystrophy: restoration of vision in RPE65 Briard dogs using an AAV serotype 4 vector that specifically targets the retinal pigmented epithelium
    F Rolling
    Universite de Nantes
    Bull Mem Acad R Med Belg 161:497-508; discussion 508-9. 2006
    ..The dog treated at a later age (30 months) did not recover retinal function or vision, suggesting that there might be a therapeutic window for the successful treatment of RPE65 -/- dogs by gene replacement therapy...
  22. ncbi request reprint Effective gene therapy with nonintegrating lentiviral vectors
    Rafael J Yáñez-Muñoz
    Molecular Immunology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
    Nat Med 12:348-53. 2006
    ..For therapeutic application to postmitotic tissues, this system substantially reduces the risk of insertional mutagenesis...
  23. ncbi request reprint Gene replacement therapy rescues photoreceptor degeneration in a murine model of Leber congenital amaurosis lacking RPGRIP
    Basil S Pawlyk
    Berman Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA 02114, USA
    Invest Ophthalmol Vis Sci 46:3039-45. 2005
    ..The current study was an investigation of whether somatic gene replacement could rescue degenerating photoreceptors in a murine model of LCA due to a defect in RPGRIP...
  24. ncbi request reprint AAV-mediated expression targeting of rod and cone photoreceptors with a human rhodopsin kinase promoter
    Shahrokh C Khani
    Department of Ophthalmology, Ross Eye Institute, State University of New York, Buffalo, New York 14215, USA
    Invest Ophthalmol Vis Sci 48:3954-61. 2007
    ..RK, also known as G protein-coupled receptor kinase 1 (GRK1), is a component of the light adaptation pathway expressed in rods and cones...
  25. ncbi request reprint Dysregulated FcepsilonRI signaling and altered Fyn and SHIP activities in Lyn-deficient mast cells
    Valerie Hernandez-Hansen
    Department of Pathology and Cancer Research and Treatment Center, University of New Mexico School of Medicine, CRF 205, 2325 Camino de Salud, Albuquerque, NM 87131, USA
    J Immunol 173:100-12. 2004
    ..The unexpected absence of the transient receptor potential channel, Trpc4, from Lyn(-/-) BMMCs may additionally contribute to their altered signaling properties...