Brain Disease Gene Therapy

Ghulam Muhammad AK, Candolfi M, King GD, Yagiz K, Foulad D, Mineharu Y, Kroeger KM, Treuer KA, Nichols WS, Sanderson NS, Yang J, Khayznikov M, Van Rooijen N, Lowenstein PR, Castro MG. Antiglioma immunological memory in response to conditional cytotoxic/immune-stimulatory gene therapy: humoral and cellular immunity lead to tumor regression. Clin Cancer Res. 2009 Oct 1;15(19):6113-27. Epub 2009 Sep 29. Click here for the PDF
Wu R, Wang H, Xia XG, Zhou H, Liu C, Castro MG, Xu Z. Nerve injection of viral vectors efficiently transfers transgenes into motor neurons and delivers RNAi therapy against ALS. Antioxid Redox Signal. 2009 Apr 3. Click here for the PDF
Curtin JF, Liu N, Candolfi M, Xiong W, Assi H, Yagiz K, Edwards MR, Michelsen KS, Kroeger KM, Liu C, Muhammad AK, Clark MC, Arditi M, Comin-Anduix B, Ribas A, Lowenstein PR, Castro MG. HMGB1 Mediates Endogenous TLR2 Activation and Brain Tumor Regression. PLoS Med. 2009 Jan 13;6(1):e10. Click here for the PDF
Curtin JF, Candolfi M, Fakhouri TM, Liu C, Alden A, Edwards M, Lowenstein PR, Castro MG. Treg depletion inhibits efficacy of cancer immunotherapy: implications for clinical trials. PLoS ONE. 2008 Apr 23;3(4):e1983. Click here for the PDF
King GD, Muhammad AK, Xiong W, Kroeger KM, Puntel M, Larocque D, Palmer D, Ng P, Lowenstein PR, Castro MG. High-capacity adenovirus vector-mediated anti-glioma gene therapy in the presence of systemic antiadenovirus immunity. J Virol. 2008 May;82(9):4680-4. Epub 2008 Feb 20. Click here for the PDF
King GD, Kroeger KM, Bresee CJ, Candolfi M, Liu C, Manalo CM, Muhammad AK, Pechnick RN, Lowenstein PR, Castro MG. Flt3L in combination with HSV1-TK-mediated gene therapy reverses brain tumor-induced behavioral deficits. Mol Ther. 2008 Apr;16(4):682-90. Epub 2008 Feb 19 Click here for the PDF
Xiong W, Candolfi M, Kroeger KM, Puntel M, Mondkar S, Larocque D, Liu C, Curtin JF, Palmer D, Ng P, Lowenstein PR, Castro MG. Immunization Against the Transgene but not the TetON Switch Reduces Expression From Gutless Adenoviral Vectors in the Brain. Mol Ther. 2008 Feb;16(2):343-351 Click here for the PDF
King GD, Kroeger KM, Bresee CJ, Candolfi M, Liu C, Manalo CM, Muhammad AG, Pechnick RN, Lowenstein PR, Castro MG. Flt3L in Combination With HSV1-TK-mediated Gene Therapy Reverses Brain Tumor-induced Behavioral Deficits. Mol Ther. 2008 Feb 19 In Press Click here for the PDF
King GD, Muhammad AK, Curtin JF, Barcia C, Puntel M, Liu C, Honig SB, Candolfi M, Mondkar S, Lowenstein PR, Castro MG.Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma model. Neuro Oncol. 2008 Jan;10(1):19-31 Click here for the PDF
Barcia C, Wawrowsky K, Barrett RJ, Liu C, Castro MG, Lowenstein PR. In Vivo Polarization of IFN-{gamma} at Kupfer and Non-Kupfer Immunological Synapses during the Clearance of Virally Infected Brain Cells. J Immunol. 2008 Feb 1;180(3):1344-1352. Click here for the PDF
Barcia C, Gerdes C, Xiong WD, Thomas CE, Liu C, Kroeger KM, Castro MG, Lowenstein PR. Immunological thresholds in neurological gene therapy: highly efficient elimination of transduced cells might be related to the specific formation of immunological synapses between T cells and virus-infected brain cells. Neuron Glia Biol. 2007 Jul 13;(2):309-322. Click here for the PDF
Lowenstein PR, Mandel RJ, Xiong WD, Kroeger K, Castro MG. Immune Responses to Adenovirus and Adeno-Associated Vectors Used for Gene Therapy of Brain Diseases: The Role of Immunological Synapses in Understanding the Cell Biology of Neuroimmune Interactions. Curr Gene Ther. 2007 Oct;7(5):347-360. Click here for the PDF
Lowenstein PR, Kroeger K, Castro MG. Immunology of neurological gene therapy: how T cells modulate viral vector-mediated therapeutic transgene expression through immunological synapses. Neurotherapeutics. 2007 Oct;4(4):715-24. Review. Click here for the PDF
Barcia C, Jimenez-Dalmaroni M, Kroeger KM, Puntel M, Rapaport AJ, Larocque D, King GD, Johnson SA, Liu C, Xiong W, Candolfi M, Mondkar S, Ng P, Palmer D, Castro MG, Lowenstein PR. One-year Expression From High-capacity Adenoviral Vectors in the Brains of Animals With Pre-existing Anti-adenoviral Immunity: Clinical Implications. Mol Ther. 2007 Dec;15(12):2154-2163. Click here for the PDF
Oh S, Pluhar GE, McNeil EA, Kroeger KM, Liu C, Castro MG, Lowenstein PR, Freese A, Ohlfest JR. Efficacy of nonviral gene transfer in the canine brain. J Neurosurg. 2007 Jul;107(1):136-44. Click here for the PDF
Candolfi M, Kroeger K, Pluhar GE, Liu C, Barcia C, Bergeron J, Puntel M, Curtin JF, McNiel EA, Freese AB, Ohlfest JR, Moore PF, Kuoy W, Lowenstein PR, Castro MG, (2007) Adenoviral-mediated gene transfer into the canine brain in vivo. Neurosurgery; 60(1):167-77 Click here for the PDF
Curtin JF, King GD, Barcia C, Liu C, Hubert FX, Guillonneau C, Josien R, Anegon I, Lowenstein PR, Castro MG."Fms-like tyrosine kinase 3 ligand recruits plasmacytoid dendritic cells to the brain." J Immunol. 2006 Mar 15;176(6):3566-77. Click here for the PDF
King GD, Curtin JF, Candolfi M, Kroeger K, Lowenstein PR, Castro MG."Gene therapy and targeted toxins for glioma." Curr Gene Ther. 2005 Dec;5(6):535-57. Click here for the PDF
Xiong W, Goverdhana S, Sciascia SA, Candolfi M, Zirger JM, Barcia C, Curtin JF, King GD, Jaita G, Liu C, Kroeger K, Agadjanian H, Medina-Kauwe L, Palmer D, Ng P, Lowenstein PR, Castro MG."Regulatable gutless adenovirus vectors sustain inducible transgene expression in the brain in the presence of an immune response against adenoviruses." J Virol. 2006 Jan;80(1):27-37. Click here for the PDF
Torres EM, Monville C, Lowenstein PR, Castro MG, Dunnett SB."Delivery of sonic hedgehog or glial derived neurotrophic factor to dopamine-rich grafts in a rat model of Parkinson's disease using adenoviral vectors Increased yield of dopamine cells is dependent on embryonic donor age." Brain Res Bull. 2005 Dec 15;68(1-2):31-41 Click here for the PDF
Curtin JF, King GD, Candolfi M, Greeno RB, Kroeger KM, Lowenstein PR, Castro MG."Combining cytotoxic and immune-mediated gene therapy to treat brain tumors." Curr Top Med Chem. 2005;5(12):1151-70. Review. Click here for the PDF
Lowenstein PR."The case for immunosuppression in clinical gene transfer." Mol Ther. 2005 Aug;12(2):185-6. Click here for the PDF
Abordo-Adesida E, Follenzi A, Barcia C, Sciascia S, Castro MG, Naldini L, Lowenstein PR."Stability of lentiviral vector-mediated transgene expression in the brain in the presence of systemic antivector immune responses." Hum Gene Ther. 2005 Jun;16(6):741-51. Click here for the PDF
Torres EM, Monville C, Lowenstein PR, Castro MG, Dunnett SB."In vivo transgene expression from an adenoviral vector is altered following a 6-OHDA lesion of the dopamine system." Brain Res Mol Brain Res. 2005 Jun 13;137(1-2):1-10. Click here for the PDF
Goverdhana S, Puntel M, Xiong W, Zirger JM, Barcia C, Curtin JF, Soffer EB, Mondkar S, King GD, Hu J, Sciascia SA, Candolfi M, Greengold DS, Lowenstein PR, Castro MG."Regulatable gene expression systems for gene therapy applications: progress and future challenges." Mol Ther. 2005 Aug;12(2):189-211. Review Click here for the PDF
Suwelack D, Hurtado-Lorenzo A, Millan E, Gonzalez-Nicolini V, Wawrowsky K, Lowenstein PR, Castro MG."Neuronal expression of the transcription factor Gli1 using the Talpha1 alpha-tubulin promoter is neuroprotective in an experimental model of Parkinson's disease." Gene Ther. 2004 Dec;11(24):1742-52. Click here for the PDF
Hurtado-Lorenzo A, Millan E, Gonzalez-Nicolini V, Suwelack D, Castro MG, Lowenstein PR."Differentiation and transcription factor gene therapy in experimental parkinson's disease: sonic hedgehog and Gli-1, but not Nurr-1, protect nigrostriatal cell bodies from 6-OHDA-induced neurodegeneration." Mol Ther. 2004 Sep;10(3):507-24. Click here for the PDF
Lowenstein PR."Input virion proteins: cryptic targets of antivector immune responses in preimmunized subjects." Mol Ther. 2004 Jun;9(6):771-4 Click here for the PDF
Lowenstein PR, Castro MG."Recent advances in the pharmacology of neurological gene therapy." Curr Opin Pharmacol. 2004 Feb;4(1):91-7. Review.
Lowenstein PR."Immunological needles in the gene therapy haystack: applying a genetic paradigm to gene therapy. "Gene Ther. 2004 Jan;11(1):1-3 Click here for the PDF
Lowenstein PR."Dendritic cells and immune responses in the central nervous system." Trends Immunol. 2002 Feb 1;23(2):70
Lowenstein PR, Castro MG."Genetic engineering within the adult brain: implications for molecular approaches to behavioral neuroscience." Physiol Behav. 2001 Aug;73(5):833-9. Review.
Castro, M. G., Hurtado-Lorenzo, A., Umana, P., Smith-Arica, J.R., Zermansky, A., Abordo-Adesida, E. and Lowenstein, P.R. (2001). Regulatable and cell-type specific transgene expression in glial cells: prospects for gene therapy for neurological disorders. Progress in Brain Research, Elsevier Science Publishers. 132: 665-691. Click here for the PDF
Castro, M. G., A. David, A. Hurtado-Lorenzo, D. Suwelack, E. Millan, T. Verakis, W. D. Xiong, X. P. Yuan and P. R. Lowenstein (2001). "Gene therapy for Parkinson's disease: recent achievements and remaining challenges." Histol Histopathol 16(4): 1225-38. Click here for the PDF
Lowenstein, P. R. (2002). "Immunology of viral-vector-mediated gene transfer into the brain: an evolutionary and developmental perspective." Trends Immunol 23(1): 23-30. Click here for the PDF
Stone, D., W. Xiong, J. C. Williams, A. David, P. R. Lowenstein and M. G. Castro (2003). "Adenovirus expression of IL-1 and NF-kappaB inhibitors does not inhibit acute adenoviral-induced brain inflammation, but delays immune system-mediated elimination of transgene expression." Mol Ther 8(3): 400-11. Click here for the PDF
Lowenstein, P. R., D. Suwelack, J. Hu, X. Yuan, M. Jimenez-Dalmaroni, S. Goverdhana and M. G. Castro (2003). "Nonneurotropic adenovirus: a vector for gene transfer to the brain and gene therapy of neurological disorders." Int Rev Neurobiol 55: 3-64. Click here for the PDF
Lowenstein, P. R. and M. G. Castro (2003). "Inflammation and adaptive immune responses to adenoviral vectors injected into the brain: peculiarities, mechanisms, and consequences." Gene Ther 10(11): 946-54. Click here for the PDF
Hurtado-Lorenzo, A., A. David, C. Thomas, M. G. Castro and P. R. Lowenstein (2003). "Use of recombinant adenovirus for gene transfer into the rat brain. Evaluation of gene transfer efficiency, toxicity, and inflammatory and immune reactions." Methods Mol Med 76: 113-33. Click here for the PDF
Castro, M. G., R. L. Cowen, I. K. Williams, A. David, M. J. Jimenez-Dalmaroni, X. Yuan, A. Birgliari, J. C. Williams, J. Hu and P. R. Lowenstein (2003). "Current and future strategies for the treatment of malignant brain tumors." Pharmacology and Therapeutics. Click here for the PDF
Cartmell, T., T. Southgate, G. S. Rees, M. G. Castro, P. R. Lowenstein and G. N. Luheshi (1999). "Interleukin-1 mediates a rapid inflammatory response after injection of adenoviral vectors into the brain." J Neurosci 19(4): 1517-23. Click here for the PDF
Lowenstein, P. R. and M. G. Castro (2002). "Progress and challenges in viral vector-mediated gene transfer to the brain." Curr Opin Mol Ther 4(4): 359-71. Click here for the PDF
Qiu, J., M. J. Whalen, P. Lowenstein, G. Fiskum, B. Fahy, R. Darwish, B. Aarabi, J. Yuan and M. A. Moskowitz (2002). "Upregulation of the Fas receptor death-inducing signaling complex after traumatic brain injury in mice and humans." J Neurosci 22(9): 3504-11. Click here for the PDF
Thomas, C.E., Edwards, P., Wickham, T.J., Castro, M.G., Lowenstein, P.R. Adenovirus binding to the coxsackievirus and adenovirus receptor or integrins is not required to elicit brain inflammation but is necessary to transduce specific neural cell types. Journal of Virology 76: 3452-3460, 2002. Click here for the PDF
Zermansky, A.J., Bolognani, Stone, D, Cowsill, C.M., Morrissey, G., Castro, M.G., and Lowenstein, P.R. 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, 2001. Click here for the PDF
Thomas, C.E., Schiedner, G., Kochanek, S., Castro, M.G., and Lowenstein, P.R. Pre-existing anti-adenoviral immunity is not a barrier to efficient and stable transduction of the brain, mediated by novel high-capacity adenovirus vectors. Human Gene Therapy, 12: 839-846, 2001. Click here for the PDF
Thomas, C., Birkett, D., Anozie, I., Castro, M.G. and Lowenstein, P.R. Acute direct adenoviral vector cytotoxity, and chronic, but not acute inflammatory responses correlate with decreased vector-mediated transgene expression in the brain. Molecular Therapy, 3: 36-46, 2001. Click here for the PDF
Gerdes, C.A., Castro, M.G. and Lowenstein, P.R. Strong promoters are the key to successful and safe gene therapy. Highly efficient adenovirus-mediated gene transfer in vivo. Molecular Therapy, 2: 330-338, 2000. Click here for the PDF
Thomas, C.E., Schiedner, G., Kochanek, S., Castro, M.G. and Lowenstein, P.R. 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, U.S.A. 97: 7482-7487, 2000. Click here for the PDF