William Pardridge

Summary

Affiliation: University of California
Country: USA

Publications

  1. pmc Tyrosine hydroxylase replacement in experimental Parkinson's disease with transvascular gene therapy
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    NeuroRx 2:129-38. 2005
  2. ncbi Blood-brain barrier delivery
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Drug Discov Today 12:54-61. 2007
  3. pmc Drug transport across the blood-brain barrier
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 32:1959-72. 2012
  4. pmc Glycemic control and chronic dosing of rhesus monkeys with a fusion protein of iduronidase and a monoclonal antibody against the human insulin receptor
    Ruben J Boado
    Department of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA
    Drug Metab Dispos 40:2021-5. 2012
  5. ncbi Molecular Trojan horses for blood-brain barrier drug delivery
    William M Pardridge
    Department of Medicine, UCLA Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Curr Opin Pharmacol 6:494-500. 2006
  6. pmc The blood-brain barrier: bottleneck in brain drug development
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    NeuroRx 2:3-14. 2005
  7. ncbi Intravenous, non-viral RNAi gene therapy of brain cancer
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    Expert Opin Biol Ther 4:1103-13. 2004
  8. ncbi Molecular biology of the blood-brain barrier
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Mol Biotechnol 30:57-70. 2005
  9. ncbi Blood-brain barrier genomics and the use of endogenous transporters to cause drug penetration into the brain
    William M Pardridge
    University of California, Los Angeles, Department of Medicine, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Curr Opin Drug Discov Devel 6:683-91. 2003
  10. ncbi Blood-brain barrier genomics
    William M Pardridge
    Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90024, USA
    Stroke 38:686-90. 2007

Research Grants

  1. Antisense imaging of brain gene expression in vivo
    William Pardridge; Fiscal Year: 2005
  2. Neurotrophin Blood/Brain Barrier Delivery in Ischemia
    William Pardridge; Fiscal Year: 2006
  3. Non-Viral Gene Targeting to the Brain
    William Pardridge; Fiscal Year: 2007
  4. AIDS Neurotherapeutics and BBB Drug Efflux
    William Pardridge; Fiscal Year: 2007
  5. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William Pardridge; Fiscal Year: 2009
  6. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William Pardridge; Fiscal Year: 2009
  7. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William M Pardridge; Fiscal Year: 2010
  8. BLOOD BRAIN BARRIER LARGE NEUTRAL AMINO ACID TRANSPORTER
    William Pardridge; Fiscal Year: 2003
  9. BLOOD/BRAIN BARRIER DRUG DELIVERY OF BDNF IN ISCHEMIA
    William Pardridge; Fiscal Year: 2002
  10. AIDS THERAPEUTICS & BLOOD-BRAIN BARRIER AZT DRUG EFFLUX
    William Pardridge; Fiscal Year: 2002

Collaborators

Detail Information

Publications79

  1. pmc Tyrosine hydroxylase replacement in experimental Parkinson's disease with transvascular gene therapy
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    NeuroRx 2:129-38. 2005
    ..A treatment for PD may be possible with dual gene therapy that seeks both to replace striatal TH gene expression with TH gene therapy, and to halt or reverse neurodegeneration of the nigro-striatal tract with neurotrophin gene therapy...
  2. ncbi Blood-brain barrier delivery
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Drug Discov Today 12:54-61. 2007
    ..Therefore, brain drug development programs of the future need to be re-configured so that drugs are formulated to enable transport into the brain via endogenous BBB transporters...
  3. pmc Drug transport across the blood-brain barrier
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 32:1959-72. 2012
    ..Knowledge on the endogenous CMT and RMT systems expressed at the BBB enable new solutions to the problem of BBB drug transport...
  4. pmc Glycemic control and chronic dosing of rhesus monkeys with a fusion protein of iduronidase and a monoclonal antibody against the human insulin receptor
    Ruben J Boado
    Department of Medicine, University of California Los Angeles, Los Angeles, CA 90024, USA
    Drug Metab Dispos 40:2021-5. 2012
    ..An intravenous glucose tolerance test performed at the end of the 6 months of chronic treatment showed no change in glucose tolerance at any dose of the HIRMAb-IDUA fusion protein...
  5. ncbi Molecular Trojan horses for blood-brain barrier drug delivery
    William M Pardridge
    Department of Medicine, UCLA Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Curr Opin Pharmacol 6:494-500. 2006
    ..The Trojan horse enables receptor-mediated delivery of the fusion protein across the BBB so that the protein drug can enter the brain and exert the desired pharmacological effect...
  6. pmc The blood-brain barrier: bottleneck in brain drug development
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    NeuroRx 2:3-14. 2005
    ..This provides the platform for CNS drug delivery programs, which should be developed in parallel with traditional CNS drug discovery efforts in the molecular neurosciences...
  7. ncbi Intravenous, non-viral RNAi gene therapy of brain cancer
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    Expert Opin Biol Ther 4:1103-13. 2004
    ..RNAi-based gene therapy can be coupled with gene therapy that replaces mutated tumour suppressor genes to build a polygenic approach to the gene therapy of cancer...
  8. ncbi Molecular biology of the blood-brain barrier
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Mol Biotechnol 30:57-70. 2005
    ..The discovery of new BBB transporters can lead to the development of new approaches to brain drug delivery using endogenous brain endothelial transporters...
  9. ncbi Blood-brain barrier genomics and the use of endogenous transporters to cause drug penetration into the brain
    William M Pardridge
    University of California, Los Angeles, Department of Medicine, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Curr Opin Drug Discov Devel 6:683-91. 2003
    ..The development of a BBB genomics program and the discovery of novel BBB transporters could lead to the invention of new approaches to solving the BBB drug delivery problem...
  10. ncbi Blood-brain barrier genomics
    William M Pardridge
    Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90024, USA
    Stroke 38:686-90. 2007
    ..The development of BBB genomics technologies enables the acquisition of a large body of new knowledge about the BBB and the brain microvasculature...
  11. pmc shRNA and siRNA delivery to the brain
    William M Pardridge
    Department of Medicine, UCLA Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    Adv Drug Deliv Rev 59:141-52. 2007
    ..The siRNA is mono-biotinylated in parallel with the production of a conjugate of the targeting MAb and streptavidin. Intravenous RNAi requires the combined use of RNAi technology and a drug targeting technology that is effective in vivo...
  12. pmc Blood-brain barrier delivery of protein and non-viral gene therapeutics with molecular Trojan horses
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    J Control Release 122:345-8. 2007
    ..Trojan horse BBB delivery systems, coupled with one of 3 different technology platforms (fusion proteins, avidin-biotin, or Trojan horse liposomes), can enable the BBB transport of virtually any large molecule drug or plasmid DNA...
  13. doi Re-engineering biopharmaceuticals for delivery to brain with molecular Trojan horses
    William M Pardridge
    Department of Medicine, University of California at Los Angeles, Los Angeles, California 90024, USA
    Bioconjug Chem 19:1327-38. 2008
    ..The development of molecular Trojan horses for BBB drug delivery allows the re-engineering of biopharmaceuticals that, owing to the BBB problem, could not otherwise be developed as new drugs for the human brain...
  14. pmc Alzheimer's disease drug development and the problem of the blood-brain barrier
    William M Pardridge
    Department of Medicine, University of California at Los Angeles, Los Angeles, CA, USA
    Alzheimers Dement 5:427-32. 2009
    ..This goal can be achieved by a reallocation of resources, and an expansion of research efforts in the pure science of BBB biology and the applied science of brain drug-targeting technology...
  15. ncbi Drug targeting to the brain
    William M Pardridge
    Department of Medicine, UCLA, Warren Hall 13 164 900 Veteran Ave, Los Angeles, CA 90024, USA
    Pharm Res 24:1733-44. 2007
    ..Molecular Trojan horses may be formulated with fusion protein technology, avidin-biotin technology, or Trojan horse liposomes to target to brain virtually any large molecule pharmaceutical...
  16. doi Biopharmaceutical drug targeting to the brain
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    J Drug Target 18:157-67. 2010
    ..The IgG fusion proteins are new bifunctional biopharmaceuticals that are both targeted to brain via transport on endogenous BBB receptors, and exert pharmacological effects in brain at the cognate receptor, ligand, or enzyme substrate...
  17. pmc Drug transport in brain via the cerebrospinal fluid
    William M Pardridge
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Fluids Barriers CNS 8:7. 2011
    ..Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium...
  18. doi Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse
    Qing Hui Zhou
    Department of Medicine, UCLA, Los Angeles, California, USA
    Drug Metab Dispos 40:329-35. 2012
    ..This work shows that a lysosomal sulfatase can be reengineered as an IgG-enzyme fusion protein that rapidly penetrates the brain after intravenous administration...
  19. ncbi Formulation of therapeutic synthetic polymers for drug and gene delivery
    William M Pardridge
    Department of Medicine, UCLA School of Medicine, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Drug Discov Today 7:1120-1. 2002
  20. ncbi William Pardridge discusses the lack of BBB research. Interview by Rebecca N. Lawrence
    William M Pardridge
    University of California, Los Angeles, 90024, USA
    Drug Discov Today 7:223-6. 2002
  21. ncbi Rat blood-brain barrier genomics. II
    Jian Yi Li
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 22:1319-26. 2002
    ..Brain vascular genomics, or BBB genomics, allows for an accelerated discovery of the gene families that are differentially expressed at the microvasculature in brain...
  22. ncbi Drug and gene delivery to the brain: the vascular route
    William M Pardridge
    Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA
    Neuron 36:555-8. 2002
    ..Novel brain drug delivery and drug targeting strategies can be developed from an understanding of the molecular and cellular biology of the brain microvascular and BBB transport processes...
  23. ncbi Targeting neurotherapeutic agents through the blood-brain barrier
    William M Pardridge
    Department of Medicine, University of California, Los Angeles, UCLA School of Medicine, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    Arch Neurol 59:35-40. 2002
    ..The future development of neurotherapeutic agents will be accelerated by the development of BBB drug-targeting technology...
  24. ncbi Brain drug targeting and gene technologies
    W M Pardridge
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095 1682, USA
    Jpn J Pharmacol 87:97-103. 2001
    ....
  25. ncbi Drug and gene targeting to the brain with molecular Trojan horses
    William M Pardridge
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    Nat Rev Drug Discov 1:131-9. 2002
    ..This article will review such molecular Trojan Horses, and the progress that has been made in the delivery of drugs and genes to the brain...
  26. ncbi Neurotrophins, neuroprotection and the blood-brain barrier
    William M Pardridge
    Department of Medicine, UCLA Warren Hall, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Curr Opin Investig Drugs 3:1753-7. 2002
    ..Neurotrophin chimeric peptides are highly neuroprotective following delayed intravenous administration, in both global and focal brain ischemia...
  27. ncbi Blood-brain barrier drug targeting enables neuroprotection in brain ischemia following delayed intravenous administration of neurotrophins
    William M Pardridge
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095 1682, USA
    Adv Exp Med Biol 513:397-430. 2002
    ..In contrast, no neuroprotection is observed following the intravenous administration of unconjugated BDNF, because the neurotrophin does not cross the BBB in vivo...
  28. ncbi Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology
    Chun Fang Xia
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, California, USA
    Pharm Res 24:2309-16. 2007
    ....
  29. ncbi Receptor-mediated delivery of an antisense gene to human brain cancer cells
    Yun Zhang
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA
    J Gene Med 4:183-94. 2002
    ..High-grade brain gliomas overexpress the epidermal growth factor receptor (EGFR) and EGFR antisense gene therapy could reduce the growth of EGFR-dependent gliomas...
  30. ncbi Blood-brain barrier drug targeting: the future of brain drug development
    William M Pardridge
    Department of Medicine UCLA School of Medicine Los Angeles, CA 90024, USA
    Mol Interv 3:90-105, 51. 2003
    ..Pardridge reviews the functions of the various known transport systems in the brain and discusses how the development of BBB drug-targeting programs in pharmaceutical and academic settings may lead to more efficacious treatments...
  31. ncbi Marked enhancement in gene expression by targeting the human insulin receptor
    Yun Zhang
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA
    J Gene Med 5:157-63. 2003
    ..The liposomes are targeted to cells with receptor-specific targeting ligands such as receptor-specific peptidomimetic monoclonal antibodies...
  32. ncbi Decline in exogenous gene expression in primate brain following intravenous administration is due to plasmid degradation
    Chun Chu
    Department of Medicine, UCLA, UCLA Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    Pharm Res 23:1586-90. 2006
    ....
  33. ncbi Intravenous nonviral gene therapy causes normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism
    Yun Zhang
    Department of Medicine, University of California, Los Angeles School of Medicine, Los Angeles, CA 90024, USA
    Hum Gene Ther 14:1-12. 2003
    ..These studies demonstrate that it is possible to normalize brain enzyme activity by intravenous administration and nonviral gene transfer...
  34. ncbi In vivo knockdown of gene expression in brain cancer with intravenous RNAi in adult rats
    Yun Zhang
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    J Gene Med 5:1039-45. 2003
    ..The limiting factor in developing RNAi therapeutics in mammals is the gene delivery system...
  35. ncbi Organ-specific gene expression in the rhesus monkey eye following intravenous non-viral gene transfer
    Yun Zhang
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Mol Vis 9:465-72. 2003
    ....
  36. ncbi Intravenous RNA interference gene therapy targeting the human epidermal growth factor receptor prolongs survival in intracranial brain cancer
    Yun Zhang
    Departments of Medicine and Neurology, University of California Los Angeles, Los Angeles, California 90024, USA
    Clin Cancer Res 10:3667-77. 2004
    ..The present study was designed to prolong survival in mice with intracranial human brain cancer with the weekly i.v. injection of nonviral gene therapy causing RNA interference (RNAi) of EGFR gene expression...
  37. ncbi Expression of the neonatal Fc receptor (FcRn) at the blood-brain barrier
    Felix Schlachetzki
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Neurochem 81:203-6. 2002
    ..The capillary endothelial FcRn may mediate the 'reverse transcytosis' of IgG in the brain to blood direction...
  38. ncbi Normalization of striatal tyrosine hydroxylase and reversal of motor impairment in experimental parkinsonism with intravenous nonviral gene therapy and a brain-specific promoter
    Yun Zhang
    Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA
    Hum Gene Ther 15:339-50. 2004
    ..These studies demonstrate that global delivery of exogenous genes to the brain is possible with intravenous nonviral gene transfer, and that ectopic gene expression is eliminated with the use of brain-specific gene promoters...
  39. ncbi Subtractive expression cloning reveals high expression of CD46 at the blood-brain barrier
    Eric V Shusta
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Neuropathol Exp Neurol 61:597-604. 2002
    ..The finding of selective expression of CD46 at the BBB is consistent with an important role played by the microvasculature in the immune surveillance of the brain...
  40. ncbi Widespread expression of an exogenous gene in the eye after intravenous administration
    Chunni Zhu
    Department of Medicine, UCLA School of Medicine, Los Angeles, California, USA
    Invest Ophthalmol Vis Sci 43:3075-80. 2002
    ....
  41. pmc Monoclonal antibody-glial-derived neurotrophic factor fusion protein penetrates the blood-brain barrier in the mouse
    Qing Hui Zhou
    Department of Medicine, University of California, Los Angeles, USA
    Drug Metab Dispos 38:566-72. 2010
    ..The brain uptake results indicate it is possible to achieve therapeutic elevations of GDNF in mouse brain with intravenous administration of the cTfRMAb-GDNF fusion protein...
  42. ncbi Gene targeting in vivo with pegylated immunoliposomes
    William M Pardridge
    University of California Los Angeles, Warren Hall, 13 164, 900 Veteran Avenue, Los Angeles, California 90024, USA
    Methods Enzymol 373:507-28. 2003
  43. pmc Genetic engineering of IgG-glucuronidase fusion proteins
    Ruben J Boado
    ArmaGen Technologies, Inc, Santa Monica, CA, USA
    J Drug Target 18:205-11. 2010
    ..This study illustrates the differential retention of functionality of IgG-enzyme fusion proteins depending on how the fusion protein is engineered...
  44. pmc Antibody-mediated targeting of siRNA via the human insulin receptor using avidin-biotin technology
    Chun Fang Xia
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    Mol Pharm 6:747-51. 2009
    ....
  45. ncbi Imaging gene expression in regional brain ischemia in vivo with a targeted [111in]-antisense radiopharmaceutical
    Toyofumi Suzuki
    University of California Los Angeles, 900 Warren Avenue, Los Angeles, CA 90024, USA
    Mol Imaging 3:356-63. 2004
    ....
  46. ncbi Molecular biology of the blood-brain barrier
    William M Pardridge
    Department of Medicine, Brain Research Institute, UCLA School of Medicine, Los Angeles, CA, USA
    Methods Mol Med 89:385-99. 2003
  47. doi Near complete rescue of experimental Parkinson's disease with intravenous, non-viral GDNF gene therapy
    Yun Zhang
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave, Los Angeles, California 90024, USA
    Pharm Res 26:1059-63. 2009
    ..The GDNF transgene expression is under the influence of the rat tyrosine hydroxylase (TH) promoter...
  48. ncbi Imaging brain amyloid of Alzheimer disease in vivo in transgenic mice with an Abeta peptide radiopharmaceutical
    Hwa Jeong Lee
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 22:223-31. 2002
    ..In conclusion, the results show that it is possible to image the Abeta amyloid burden in the brain in vivo with an amyloid imaging agent, provided the molecule is conjugated to a blood-brain barrier drug-targeting system...
  49. ncbi Enhanced neuroprotective effects of basic fibroblast growth factor in regional brain ischemia after conjugation to a blood-brain barrier delivery vector
    Bi Wei Song
    Department of Pathology, University of California Los Angeles, School of Medicine, Los Angeles, California 90024, USA
    J Pharmacol Exp Ther 301:605-10. 2002
    ..In conclusion, neuroprotection in regional brain ischemia is possible following the delayed intravenous injection of low doses of bFGF providing the neurotrophin is conjugated to a BBB drug-targeting system...
  50. ncbi Pharmacokinetics and brain uptake of biotinylated basic fibroblast growth factor conjugated to a blood-brain barrier drug delivery system
    Dafang Wu
    Department of Pathology, UCLA School of Medicine, CA 90095, USA
    J Drug Target 10:239-45. 2002
    ..The re-formulation of bFGF to enable receptor-mediated transcytosis across the BBB may improve the therapeutic index of this neurotrophin as a neuroprotective agent...
  51. ncbi Glucose deprivation and hypoxia increase the expression of the GLUT1 glucose transporter via a specific mRNA cis-acting regulatory element
    Ruben J Boado
    Department of Medicine and Brain Research Institute, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Neurochem 80:552-4. 2002
    ..Data presented here suggest that the GLUT1 CAE2181-2190 participates in the increase of GLUT1 gene expression in glucose deprivation and hypoxia...
  52. ncbi Developmental regulation of the rabbit blood-brain barrier LAT1 large neutral amino acid transporter mRNA and protein
    Ruben J Boado
    Department of Medicine, University of California at Los Angeles, CA 90024, USA
    Pediatr Res 55:557-60. 2004
    ..The dissociation between LAT1 protein and mRNA levels in development is consistent with posttranscriptional regulation of BBB LAT1 gene expression...
  53. ncbi Site-directed mutagenesis of cysteine residues of large neutral amino acid transporter LAT1
    Ruben J Boado
    Department of Medicine, UCLA Warren Hall 13 164, 900 Veteran Ave, Los Angeles, CA 90024, USA
    Biochim Biophys Acta 1715:104-10. 2005
    ..These studies show that the Cys439 residue of LAT1 plays a significant role in either folding or insertion of the transporter protein in the plasma membrane...
  54. ncbi Human LAT1 single nucleotide polymorphism N230K does not alter phenylalanine transport
    Ruben J Boado
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Mol Genet Metab 83:306-11. 2004
    ..These studies demonstrate that the only known SNP in the open reading frame of human LAT1 has no effect on the kinetics of large neutral amino acid transport via this carrier...
  55. ncbi P-glycoprotein and caveolin-1alpha in endothelium and astrocytes of primate brain
    Felix Schlachetzki
    Department of Medicine, UCLA, Warren Hall 13 164, 900 Veteran Ave Los Angeles, CA 90024, USA
    Neuroreport 14:2041-6. 2003
    ..These findings suggest that P-gp and caveolin-1alpha share a broad spectrum of cellular expression and may play a role in drug transport within the brain in addition to the BBB...
  56. ncbi Organ-specific expression of the lacZ gene controlled by the opsin promoter after intravenous gene administration in adult mice
    Chunni Zhu
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    J Gene Med 6:906-12. 2004
    ..Adult transgenics' is possible with the acute expression of an exogenous gene that is administered to adult animals, providing the transgene can be effectively delivered to distant sites following an intravenous administration...
  57. ncbi Hypoxia induces de-stabilization of the LAT1 large neutral amino acid transporter mRNA in brain capillary endothelial cells
    Ruben J Boado
    Department of Medicine, UCLA School of Medicine, Warren Hall 13 164, 900 Veteran Avenue, Los Angeles, CA 90024, USA
    J Neurochem 85:1037-42. 2003
    ..These studies are consistent with post-transcriptional de-stabilization of the LAT1 large neutral amino acid transporter in hypoxia...
  58. ncbi Absence of toxicity of chronic weekly intravenous gene therapy with pegylated immunoliposomes
    Yu feng Zhang
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Pharm Res 20:1779-85. 2003
    ..Therefore, the purpose of the present study was to examine for toxic side effects of the chronic weekly intravenous administration of plasmid DNA delivered with a nonviral gene transfer method using pegylated immunoliposomes (PIL)...
  59. ncbi Site-directed mutagenesis of rabbit LAT1 at amino acids 219 and 234
    Ruben J Boado
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Neurochem 84:1322-31. 2003
    ..These studies show that marked changes in the affinity and capacity of the LAT1 are caused by single nucleotide polymorphisms and that phenotype can be restored with a double mutation...
  60. ncbi Global non-viral gene transfer to the primate brain following intravenous administration
    Yun Zhang
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90024, USA
    Mol Ther 7:11-8. 2003
    ..Widespread neuronal expression of the beta-galactosidase gene in primate brain was demonstrated by both histochemistry and confocal microscopy. This approach makes feasible reversible adult transgenics in 24 hours...
  61. ncbi Imaging gene expression in the brain in vivo in a transgenic mouse model of Huntington's disease with an antisense radiopharmaceutical and drug-targeting technology
    Hwa Jeong Lee
    Department of Medicine, UCLA School of Medicine, 90024, USA
    J Nucl Med 43:948-56. 2002
    ..The current studies describe the production of 16-mer peptide nucleic acid (PNA) that is antisense around the methionine initiation codon of the huntingtin gene of Huntington's disease (HD)...
  62. ncbi Vascular genomics of the human brain
    Eric V Shusta
    Departments of Medicine and Surgery Neurosurgery, UCLA School of Medicine, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 22:245-52. 2002
    ....
  63. ncbi Delivery of beta-galactosidase to mouse brain via the blood-brain barrier transferrin receptor
    Yun Zhang
    Department of Medicine, University of California Los Angeles, 90024, USA
    J Pharmacol Exp Ther 313:1075-81. 2005
    ..Fusion proteins comprised of BBB targeting antibodies and recombinant enzymes could be therapeutic in the treatment of the brain in human lysosomal storage disorders...
  64. pmc Blood-brain barrier genomics and cloning of a novel organic anion transporter
    Chun Chu
    Department of Medicine, UCLA, Los Angeles, California 90024, USA
    J Cereb Blood Flow Metab 28:291-301. 2008
    ..Blood-brain barrier-specific anion transporter type 1 is a novel organic anion transporter that is a sodium-independent exchanger that may participate in the active efflux of iodothyronines and steroid conjugates at the BBB...
  65. ncbi Comparison of cDNA and genomic forms of tyrosine hydroxylase gene therapy of the brain with Trojan horse liposomes
    Chun Fang Xia
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    J Gene Med 9:605-12. 2007
    ..The brain expression of a rat tyrosine hydroxylase (TH) cDNA is compared to the brain expression of a plasmid DNA encoding the 18 kb rat TH gene...
  66. ncbi Antisense gene therapy of brain cancer with an artificial virus gene delivery system
    Yun Zhang
    Department of Medicine, UCLA School of Medicine, Los Angeles, California 90024, USA
    Mol Ther 6:67-72. 2002
    ..The lifespan of the mice treated weekly with an intravenous administration of the EGFR antisense gene therapy packaged within the artificial virus is increased 100% relative to mice treated either with a luciferase gene or with saline...
  67. pmc Neuroprotection with a brain-penetrating biologic tumor necrosis factor inhibitor
    Qing Hui Zhou
    Department of Medicine, University of California, Los Angeles, California, USA
    J Pharmacol Exp Ther 339:618-23. 2011
    ..In conclusion, a biologic TNF inhibitor is neuroprotective after intravenous administration in a mouse model of neurodegeneration, providing that the TNF decoy receptor is reengineered to cross the BBB...
  68. pmc Chronic dosing of mice with a transferrin receptor monoclonal antibody-glial-derived neurotrophic factor fusion protein
    Qing Hui Zhou
    Department of Medicine, UCLA, Los Angeles, CA 90024, USA
    Drug Metab Dispos 39:1149-54. 2011
    ..The study shows no toxic side effects from chronic cTfRMAb-GDNF systemic treatment and the absence of neutralizing antibodies in vivo...
  69. pmc Brain-penetrating tumor necrosis factor decoy receptor in the mouse
    Qing Hui Zhou
    Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
    Drug Metab Dispos 39:71-6. 2011
    ..This new IgG-TNFR fusion protein can be tested in mouse models of brain diseases in which TNF╬▒ plays a pathologic role...
  70. ncbi Humanization of anti-human insulin receptor antibody for drug targeting across the human blood-brain barrier
    Ruben J Boado
    ArmaGen Technologies, Inc, Santa Monica, California 90401, USA
    Biotechnol Bioeng 96:381-91. 2007
    ..The humanized HIRMAb may be used as a brain drug and gene delivery system for the targeting of large molecule therapeutics across the BBB in humans...
  71. ncbi Why is the global CNS pharmaceutical market so under-penetrated?
    William M Pardridge
    Drug Discov Today 7:5-7. 2002
  72. ncbi Genetic engineering of a lysosomal enzyme fusion protein for targeted delivery across the human blood-brain barrier
    Ruben J Boado
    ArmaGen Technologies, Inc, Santa Monica, California 90401, USA
    Biotechnol Bioeng 99:475-84. 2008
    ..The HIRMAb-IDUA fusion protein is a new treatment for Hurler's syndrome, which has been specifically engineered to cross the human BBB...
  73. ncbi Imaging endogenous gene expression in brain cancer in vivo with 111In-peptide nucleic acid antisense radiopharmaceuticals and brain drug-targeting technology
    Toyofumi Suzuki
    College of Pharmacy, Nihon University, Chiba, Japan
    J Nucl Med 45:1766-75. 2004
    ....
  74. ncbi Genetic engineering, expression, and activity of a fusion protein of a human neurotrophin and a molecular Trojan horse for delivery across the human blood-brain barrier
    Ruben J Boado
    ArmaGen Technologies Inc, Santa Monica, California, USA
    Biotechnol Bioeng 97:1376-86. 2007
    ..Neurotrophins, such as BDNF, can be re-formulated to enable these molecules to cross the human BBB, and such fusion proteins represent a new class of human neurotherapeutics...
  75. ncbi The Ro52/SS-A autoantigen has elevated expression at the brain microvasculature
    Eric V Shusta
    Department of Chemical and Biological Engineering, University of Wisconsin, Madison, WI 53706, USA
    Neuroreport 14:1861-5. 2003
    ..The selective expression of Ro52/SS-A in brain at the microvasculature may play a role in brain vascular involvement in autoimmune diseases...
  76. pmc Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and abeta fibril disaggregation
    Ruben J Boado
    ArmaGen Technologies, Incorporated, Santa Monica, California, USA
    Bioconjug Chem 18:447-55. 2007
    ..This fusion protein is a new antibody-based therapeutic for Alzheimer's disease that is specifically engineered to cross the human blood-brain barrier in both directions...
  77. ncbi Monoclonal antibody radiopharmaceuticals: cationization, pegylation, radiometal chelation, pharmacokinetics, and tumor imaging
    Hwa Jeong Lee
    College of Pharmacy, Ewha Womans University, Seoul 120 750, South Korea
    Bioconjug Chem 14:546-53. 2003
    ....
  78. ncbi Gene therapy of the brain: the trans-vascular approach
    Felix Schlachetzki
    Department of Neurology, University of Regensburg, Germany
    Neurology 62:1275-81. 2004
    ..Global and reversible expression of therapeutic genes in the human brain without surgery and without viral vectors is now possible...
  79. doi Genetic engineering, expression, and activity of a chimeric monoclonal antibody-avidin fusion protein for receptor-mediated delivery of biotinylated drugs in humans
    Ruben J Boado
    ArmaGen Technologies, Inc, Santa Monica, California 90401, USA
    Bioconjug Chem 19:731-9. 2008
    ..In summary, the HIRMAb-AV fusion protein is a new drug targeting system for humans that can be adapted to monobiotinylated drugs or nucleic acids...

Research Grants35

  1. Antisense imaging of brain gene expression in vivo
    William Pardridge; Fiscal Year: 2005
    ..This technology could be extended to humans and to other organs. At present, there is no parallel technology that enables the non-invasive in vivo imaging of "any gene in any person," which is the goal of this work. ..
  2. Neurotrophin Blood/Brain Barrier Delivery in Ischemia
    William Pardridge; Fiscal Year: 2006
    ..This work will attempt to show that neurogenesis in the adult brain subjected to ischemia can be induced with the intravenous administration of BDNF and/or bFGF, providing the neurotrophin is enabled to cross the intact BBB in vivo. ..
  3. Non-Viral Gene Targeting to the Brain
    William Pardridge; Fiscal Year: 2007
    ....
  4. AIDS Neurotherapeutics and BBB Drug Efflux
    William Pardridge; Fiscal Year: 2007
    ..This work provides the basis for future drug discovery of AET blockers, which can be used as co-drugs to increase CNS penetration of HAART drugs. ..
  5. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William Pardridge; Fiscal Year: 2009
    ..The present research will test in AD transgenic mice the efficacy of a new genetically engineered fusion antibody that both crosses the BBB via receptor-mediation and binds and disaggregates Ab amyloid plaque of AD. ..
  6. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William Pardridge; Fiscal Year: 2009
    ..The present research will test in AD transgenic mice the efficacy of a new genetically engineered fusion antibody that both crosses the BBB via receptor-mediation and binds and disaggregates A amyloid plaque of AD. ..
  7. Monoclonal Antibody Drug Development for Alzheimer?s Disease
    William M Pardridge; Fiscal Year: 2010
    ..The present research will test in AD transgenic mice the efficacy of a new genetically engineered fusion antibody that both crosses the BBB via receptor-mediation and binds and disaggregates Ab amyloid plaque of AD. ..
  8. BLOOD BRAIN BARRIER LARGE NEUTRAL AMINO ACID TRANSPORTER
    William Pardridge; Fiscal Year: 2003
    ..These studies will provide new molecular biological information on a crucial transporter at the blood-brain barrier that regulates the supply in the brain of essential amino acids. ..
  9. BLOOD/BRAIN BARRIER DRUG DELIVERY OF BDNF IN ISCHEMIA
    William Pardridge; Fiscal Year: 2002
    ..This brain-drug delivery strategy can be ultimately used in humans because recent studies have developed human- specific BBB transport vectors. ..
  10. AIDS THERAPEUTICS & BLOOD-BRAIN BARRIER AZT DRUG EFFLUX
    William Pardridge; Fiscal Year: 2002
    ..abstract_text> ..
  11. REGULATION OF BBB GLUT1 GLUCOSE TRANSPORTER
    William Pardridge; Fiscal Year: 2002
    ..These studies will provide insight into molecular mechanisms of regulation of a step crucial to the maintenance of cerebral intermediary metabolism, i.e., the continuous transport of glucose across the blood-brain barrier in vivo. ..
  12. Neurotrophin Drug Development for Parkinson's Disease
    William M Pardridge; Fiscal Year: 2010
    ....