Ronald Mandel

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. ncbi request reprint CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease
    Ronald J Mandel
    University of Florida, College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA
    Curr Opin Mol Ther 12:240-7. 2010
  2. pmc Viral vectors for in vivo gene transfer in Parkinson's disease: properties and clinical grade production
    Ronald J Mandel
    Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Exp Neurol 209:58-71. 2008
  3. ncbi request reprint Clinical trials in neurological disorders using AAV vectors: promises and challenges
    Ronald J Mandel
    University of Florida College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA
    Curr Opin Mol Ther 6:482-90. 2004
  4. ncbi request reprint Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders
    Ronald J Mandel
    Department of Neuroscience, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Mol Ther 13:463-83. 2006
  5. pmc Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA
    Mol Ther 17:980-91. 2009
  6. pmc Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice
    Edgardo Rodriguez-Lebron
    Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, 32610 0244, USA
    Mol Ther 12:618-33. 2005
  7. ncbi request reprint rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson's disease
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Exp Neurol 207:289-301. 2007
  8. pmc Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain
    Carmen S Peden
    University of Florida College of Medicine, P O Box 100244, Gainesville, FL 32610, USA
    J Virol 78:6344-59. 2004
  9. pmc α-Synuclein expression in rat substantia nigra suppresses phospholipase D2 toxicity and nigral neurodegeneration
    Oleg S Gorbatyuk
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, USA
    Mol Ther 18:1758-68. 2010
  10. ncbi request reprint Recombinant adeno-associated viral vectors in the nervous system
    Corinna Burger
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 16:781-91. 2005

Collaborators

Detail Information

Publications42

  1. ncbi request reprint CERE-110, an adeno-associated virus-based gene delivery vector expressing human nerve growth factor for the treatment of Alzheimer's disease
    Ronald J Mandel
    University of Florida, College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA
    Curr Opin Mol Ther 12:240-7. 2010
    ..CERE-110 has passed phase I clinical testing and a multicenter phase II clinical trial has commenced. CERE-110 is a promising candidate for the treatment of AD...
  2. pmc Viral vectors for in vivo gene transfer in Parkinson's disease: properties and clinical grade production
    Ronald J Mandel
    Department of Neuroscience, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Exp Neurol 209:58-71. 2008
    ..The viral vector properties themselves combined with physiological product formulations facilitate long-term storage and direct in vivo administration...
  3. ncbi request reprint Clinical trials in neurological disorders using AAV vectors: promises and challenges
    Ronald J Mandel
    University of Florida College of Medicine, Department of Neuroscience, PO Box 100244, Gainesville, FL 32610, USA
    Curr Opin Mol Ther 6:482-90. 2004
    ..Other gene therapy treatment strategies for PD and other disorders, such as amyotrophic lateral sclerosis, are also on the horizon...
  4. ncbi request reprint Recombinant adeno-associated viral vectors as therapeutic agents to treat neurological disorders
    Ronald J Mandel
    Department of Neuroscience, and McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Mol Ther 13:463-83. 2006
    ..Therefore, we will review the currently available preclinical data using rAAV in animal models of central nervous system (CNS) disorders. Moreover, potential caveats for rAAV-based gene therapy in the CNS are also presented...
  5. pmc Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA
    Mol Ther 17:980-91. 2009
    ..Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats...
  6. pmc Intrastriatal rAAV-mediated delivery of anti-huntingtin shRNAs induces partial reversal of disease progression in R6/1 Huntington's disease transgenic mice
    Edgardo Rodriguez-Lebron
    Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, 32610 0244, USA
    Mol Ther 12:618-33. 2005
    ..These results suggest that a reduction in the levels of striatal mHtt can ameliorate the HD phenotype of R6/1 mice...
  7. ncbi request reprint rAAV-mediated nigral human parkin over-expression partially ameliorates motor deficits via enhanced dopamine neurotransmission in a rat model of Parkinson's disease
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Exp Neurol 207:289-301. 2007
    ....
  8. pmc Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain
    Carmen S Peden
    University of Florida College of Medicine, P O Box 100244, Gainesville, FL 32610, USA
    J Virol 78:6344-59. 2004
    ..Regardless, the data show that the presence of high levels of NAb against wt AAV can reduce rAAV-mediated transduction in the brain and should be accounted for in future experiments utilizing this vector...
  9. pmc α-Synuclein expression in rat substantia nigra suppresses phospholipase D2 toxicity and nigral neurodegeneration
    Oleg S Gorbatyuk
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, Florida, USA
    Mol Ther 18:1758-68. 2010
    ..Our data also demonstrate that it is possible to use viral-mediated gene transfer to study gene interactions in vivo...
  10. ncbi request reprint Recombinant adeno-associated viral vectors in the nervous system
    Corinna Burger
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA
    Hum Gene Ther 16:781-91. 2005
    ....
  11. ncbi request reprint Changes in transcription within the CA1 field of the hippocampus are associated with age-related spatial learning impairments
    Corinna Burger
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Box 100266, Gainesville, FL 32610, USA
    Neurobiol Learn Mem 87:21-41. 2007
    ..Finally, these 50 genes were functioning in the context of an aging CA1 region where over 200 genes was found to be differentially expressed compared to a young CA1...
  12. ncbi request reprint Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system
    Corinna Burger
    Department of Molecular Genetics and Microbiology, University of Florida, Gainesville 32610, USA
    Mol Ther 10:302-17. 2004
    ..Retrograde transport of rAAV1 and rAAV5 was also observed in particular CNS areas. These results suggest that vectors based on distinct AAV serotypes can be chosen for specific applications in the nervous system...
  13. ncbi request reprint Development of gene therapy for neurological disorders
    Fredric P Manfredsson
    Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32611, USA
    Discov Med 9:204-11. 2010
    ..This interface dictates the proper design of clinical trials that are capable of testing whether the treatment is actually successful...
  14. pmc In vivo RNAi-mediated alpha-synuclein silencing induces nigrostriatal degeneration
    Oleg S Gorbatyuk
    Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gene Therapy Center Cancer Genetics Research Complex, Building 1376 1376 Mowry Road, Room CG 208 Gainesville, FL 32610, USA
    Mol Ther 18:1450-7. 2010
    ..Our data show that alpha-syn plays an important role in the rat SNc and suggest that both up- and downregulation of wild-type alpha-syn expression increase the risk of nigrostriatal pathology...
  15. ncbi request reprint Hypothalamic rAAV-mediated GDNF gene delivery ameliorates age-related obesity
    Nihal Tumer
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Neurobiol Aging 27:459-70. 2006
    ..Our observations in aged rats suggest that GDNF may be especially effective in reducing obesity in aged obese rats...
  16. ncbi request reprint Time course of transgene expression after intrastriatal pseudotyped rAAV2/1, rAAV2/2, rAAV2/5, and rAAV2/8 transduction in the rat
    Sharon Reimsnider
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    Mol Ther 15:1504-11. 2007
    ..The inflammatory response to these rAAV vectors was present up to 4 weeks after transduction but was not apparent 9 months post injection. Thus, rAAV-mediated transgene expression begins earlier than previously thought...
  17. ncbi request reprint Neonatal intraperitoneal or intravenous injections of recombinant adeno-associated virus type 8 transduce dorsal root ganglia and lower motor neurons
    Kevin D Foust
    Department of Pediatrics, Evelyn F and William L McKnight Brian Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Hum Gene Ther 19:61-70. 2008
    ..Our data suggest that systemic injection of rAAV8 is not an effective delivery route to target lower motor neurons, but could be useful for targeting sensory pathways in chronic pain...
  18. ncbi request reprint Recombinant adeno-associated virus-mediated global anterograde delivery of glial cell line-derived neurotrophic factor to the spinal cord: comparison of rubrospinal and corticospinal tracts in the rat
    Kevin D Foust
    Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL 32611, USA
    Hum Gene Ther 19:71-82. 2008
    ..Spinal cord GDNF levels were elevated at distances up to 72 mm from the injection sites, and confirmed that RST-related GDNF transport to spinal cord surpassed CST-associated delivery...
  19. pmc The phosphorylation state of Ser-129 in human alpha-synuclein determines neurodegeneration in a rat model of Parkinson disease
    Oleg S Gorbatyuk
    Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL 32610, USA
    Proc Natl Acad Sci U S A 105:763-8. 2008
    ..This suggests possible new therapeutic targets for Parkinson Disease...
  20. pmc Genome-wide analysis of aging and learning-related genes in the hippocampal dentate gyrus
    Corinna Burger
    Department of Neurology, University of Wisconsin Madison, University of Florida, Gainesville, FL 32610, USA
    Neurobiol Learn Mem 89:379-96. 2008
    ..This long list of genes constitutes a starting tool to elucidating the molecular pathways involved in learning and memory formation...
  21. pmc Tight Long-term dynamic doxycycline responsive nigrostriatal GDNF using a single rAAV vector
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida 32611, USA
    Mol Ther 17:1857-67. 2009
    ..Therefore, this single rAAV vector system meets most of the requirements for an experimental reagent for treatment of PD...
  22. ncbi request reprint Systemic mannitol-induced hyperosmolality amplifies rAAV2-mediated striatal transduction to a greater extent than local co-infusion
    Corinna Burger
    Department of Molecular Genetics and Microbiology, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
    Mol Ther 11:327-31. 2005
    ..In conclusion, we have demonstrated that systemic coadministration of mannitol significantly enhances transgene spread of rAAV2 viral delivery in the brain to a much greater degree than local coadministration...
  23. ncbi request reprint Gene therapy for pyruvate dehydrogenase E1alpha deficiency using recombinant adeno-associated virus 2 (rAAV2) vectors
    Renius Owen
    Department of Pediatrics, the General Clinical Research Center, University of Florida, Gainesville, Florida 32610, USA
    Mol Ther 6:394-9. 2002
    ..These studies provide the basis for future efforts to develop a recombinant AAV (rAAV)-based gene therapy approach for the correction of PDC deficiency...
  24. ncbi request reprint A method for a more complete in vitro Parkinson's model: slice culture bioassay for modeling maintenance and repair of the nigrostriatal circuit
    Sean M Kearns
    Department of Neuroscience, The McKnight Brain Institute, Shands Cancer Center, Program in Stem Cell Biology and Regenerative Medicine, University of Florida, Gainesville, FL 32610, USA
    J Neurosci Methods 157:1-9. 2006
    ..This unique culture system presents a new approach for modeling Parkinson's disease in vitro, and provides a potentially useful new method for screening cell and molecular therapies for neurodegenerative diseases...
  25. ncbi request reprint Gene therapy for neurological disorders: challenges and future prospects for the use of growth factors for the treatment of Parkinson's disease
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA
    Curr Gene Ther 9:375-88. 2009
    ..However, gene regulation systems pose unique safety issues and we will discuss these in detail. It is our view that GDFLs still remain as a promising therapeutic approach for PD...
  26. pmc Striatal readministration of rAAV vectors reveals an immune response against AAV2 capsids that can be circumvented
    Carmen S Peden
    Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida, USA
    Mol Ther 17:524-37. 2009
    ..We conclude that intracellular processing of AAV capsids after transduction is the immunogenic antigen and capsid serotypes that are processed more quickly than rAAV2/2 are less immunogenic...
  27. ncbi request reprint Adeno-associated virus-mediated aspartoacylase gene transfer to the brain of knockout mouse for canavan disease
    Reuben Matalon
    Department of Pediatrics, Galveston, Texas 77555 0359, USA
    Mol Ther 7:580-7. 2003
    ..MRS revealed that in vivo NAA levels were also reduced. These data indicate that rAAV-mediated ASPA delivery may be an interesting avenue for the treatment of CD...
  28. ncbi request reprint Anterograde delivery of brain-derived neurotrophic factor to striatum via nigral transduction of recombinant adeno-associated virus increases neuronal death but promotes neurogenic response following stroke
    Elin Gustafsson
    Section of Restorative Neurology, Wallenberg Neuroscience Center, University of Lund, BMC A 11 SE 221 84 Lund, Sweden
    Eur J Neurosci 17:2667-78. 2003
    ..Concomitantly, brain-derived neurotrophic factor potentiates the stroke-induced neurogenic response, at least at early stages...
  29. ncbi request reprint Elevated GDNF levels following viral vector-mediated gene transfer can increase neuronal death after stroke in rats
    Andreas Arvidsson
    Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11 SE 221 84, Lund, Sweden
    Neurobiol Dis 14:542-56. 2003
    ..Our findings also underscore the need for quantitative assessment of long-term neuronal survival and behavioral changes to evaluate the therapeutic potential of factors such as GDNF...
  30. ncbi request reprint Neuropathological and behavioral consequences of adeno-associated viral vector-mediated continuous intrastriatal neurotrophin delivery in a focal ischemia model in rats
    Gunnar Andsberg
    Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, Lund, Sweden
    Neurobiol Dis 9:187-204. 2002
    ..We observe that intrastriatal delivery of NGF and BDNF using a viral vector system can mitigate, albeit only moderately, neuronal death following stroke, which leads to detectable functional sparing...
  31. pmc 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
    Pedro R Lowenstein
    Gene Therapeutics Research Institute, Cedars Sinai Medical Center, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90048, USA
    Curr Gene Ther 7:347-60. 2007
    ....
  32. ncbi request reprint Reversal of dyskinesias in an animal model of Parkinson's disease by continuous L-DOPA delivery using rAAV vectors
    Thomas Carlsson
    Wallenberg Neuroscience Center, Division of Neurobiology, Lund University, Lund, Sweden
    Brain 128:559-69. 2005
    ..These findings form a strong basis for replacing, or supplementing, conventional systemic L-DOPA therapy by continuous intrastriatal DOPA using in vivo gene transfer in the treatment of patients with advanced Parkinson's disease...
  33. ncbi request reprint Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system
    Deniz Kirik
    Wallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, 221 84, Lund, Sweden
    J Neurosci 22:2780-91. 2002
    ..Targeted overexpression of alpha-synuclein in the nigrostriatal system may provide a new animal model of Parkinson's disease that reproduces some of the cardinal pathological, neurochemical, and behavioral features of the human disease...
  34. ncbi request reprint Continuous low-level glial cell line-derived neurotrophic factor delivery using recombinant adeno-associated viral vectors provides neuroprotection and induces behavioral recovery in a primate model of Parkinson's disease
    Andisheh Eslamboli
    Department of Experimental Psychology, University of Cambridge, Cambridge CB2 3EB, United Kingdom
    J Neurosci 25:769-77. 2005
    ..We conclude that when delivered continuously, a low level of GDNF in the striatum (approximately threefold above baseline) is sufficient to provide optimal functional outcome...
  35. ncbi request reprint Long-term consequences of human alpha-synuclein overexpression in the primate ventral midbrain
    Andisheh Eslamboli
    Department of Experimental Psychology, Downing Street, Cambridge, UK
    Brain 130:799-815. 2007
    ....
  36. pmc Reversal of motor impairments in parkinsonian rats by continuous intrastriatal delivery of L-dopa using rAAV-mediated gene transfer
    Deniz Kirik
    Wallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, BMC A11, S 221 84, Lund, Sweden
    Proc Natl Acad Sci U S A 99:4708-13. 2002
    ....
  37. pmc Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease
    Deniz Kirik
    Wallenberg Neuroscience Center, Department of Physiological Sciences, Division of Neurobiology, Lund University, BMC A11, 221 84 Lund, Sweden
    Proc Natl Acad Sci U S A 100:2884-9. 2003
    ..This model offers new opportunities for the study of pathogenetic mechanisms and exploration of new therapeutic targets of particular relevance to human PD...
  38. ncbi request reprint Suppression of insult-induced neurogenesis in adult rat brain by brain-derived neurotrophic factor
    Elin Larsson
    Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, BMC A 11 SE 221 84, Lund, Sweden
    Exp Neurol 177:1-8. 2002
    ..Our data indicate that long-term delivery of a neurotrophic factor, which is considered as a novel neuroprotective strategy for human brain diseases, may attenuate intrinsic neuroregenerative responses...
  39. ncbi request reprint Recombinant adeno-associated viral vector (rAAV) delivery of GDNF provides protection against 6-OHDA lesion in the common marmoset monkey (Callithrix jacchus)
    Andisheh Eslamboli
    Department of Experimental Psychology, Downing Street, University of Cambridge, CB2 3EB, Cambridge, UK
    Exp Neurol 184:536-48. 2003
    ..Therefore, our study provides evidence for the behavioural and anatomical efficacy of GDNF delivered via an rAAV vector as a possible treatment for Parkinson's disease...
  40. ncbi request reprint Comprehensive screening of a North American Parkinson's disease cohort for LRRK2 mutation
    Janel Johnson
    Laboratory of Neurogenetics, National Institute on Aging, Porter Neuroscience Research Center, National Institutes of Health, Bethesda, MD 20892, USA
    Neurodegener Dis 4:386-91. 2007
    ..Recently, mutations in LRRK2 encoding the protein dardarin have been linked to an autosomal dominant form of parkinsonism...
  41. ncbi request reprint Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data
    Hon Chung Fung
    Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA
    Lancet Neurol 5:911-6. 2006
    ....
  42. pmc Unexpected off-targeting effects of anti-huntingtin ribozymes and siRNA in vivo
    Eileen M Denovan-Wright
    Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
    Neurobiol Dis 29:446-55. 2008
    ..These findings have important implications in the development of therapeutic RNAi for the treatment of neurological disease...

Research Grants7

  1. rAAV-mediated knockdown for Huntington's disease
    Ronald Mandel; Fiscal Year: 2007
    ....
  2. Global spinal cord trophic factor delivery using intracerebral rAAV in ALS rats
    Ronald Mandel; Fiscal Year: 2007
    ..These data may have general implications for spinal cord injuries and ALS in particular. ..
  3. rAAV-mediated knockdown for Huntington's disease
    Ronald J Mandel; Fiscal Year: 2010
    ..abstract_text> ..