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Our Research

All of our projects depend on the creation and advancement of direct infusion of drugs and therapies into the brain.

We have developed a technique in which nanoparticles, including viral vectors and liposomes can be infused directly into brain tumors to give enhanced drug efficacy.

Parkinson's Disease

For many years, and continuing still, we have been working on development of direct drug delivery into the brain including cell transplantation, gene transfer and growht factor infusions for Parkinson's disease.

Niemann-Pick

Through gene therapy, we are working to eliminate the gene responsible for Niemann-Pick (acid sphingomyelinase).

Dyskinesia

By studying the effects of L-Dopa on the brain, we are developing gene therapy for L-Dopa-induced dyskinesia.

Selected Publications

2009

Yin, D., F. E. Valles, et al. (2009).
Striatal volume differences between non-human and human primates." J Neurosci Methods 176(2): 200-5.

2008

Dickinson, PJ, LeCouteur RA, Higgins RJ, Bringas JR, Roberts B, Larson, RF, Yamashita, Y, Krauze, MT, Noble, CO, Drummond, D, Kirpotin, DB, Park, JW, Mitchel S Berger, MB, Bankiewicz KS., 2008.
Convection enhanced delivery of liposomes containing CPT-11 monitored with real time magnetic resonance imaging in a canine large animal model system. Journal of Neurosurgery (in press).

Eberling JL, Jagust WJ, Christine CW, Starr P, Larson P, Bankiewicz KS, and Michael J. Aminoff MJ., 2008.
Results from a Phase I Safety Trial of hAADC Gene Therapy for Parkinson's Disease. Neurology (in press).

Fiandaca, M. S., V. Varenika, et al. (2008).
"Real-time MR imaging of adeno-associated viral vector delivery to the primate brain." Neuroimage.

Fiandaca, M., Forsayeth, J., and Bankiewicz, K., 2008.
Current status of gene therapy trials for Parkinson's disease. Exp Neurol 209, 51-57

Fiandaca, M. S., Forsayeth, J. R., Dickinson, P. J., and Bankiewicz, K. S., 2008.
Image-guided convection-enhanced delivery platform in the treatment of neurological diseases. Neurotherapeutics 5, 123-127

Varenika V, Dickinson P, Bringas J, LeCouteur R, Higgins R, Park J, Fiandaca MS, Berger M, Sampson J and Bankiewicz KS., 2008.
Real-Time Imaging of CED in the Brain Permits Detection of Infusate Leakage. Journal of Neurosurgery (in press).

Hadaczek, P., J. Forsayeth, et al. (2008).
"Transduction of non-human primate brain with adeno-associated virus serotype 1: vector trafficking and immune response." Hum Gene Ther.

Herzog, C. D., B. Dass, et al. (2008).
"Transgene expression, bioactivity, and safety of CERE-120 (AAV2-neurturin) following delivery to the monkey striatum." Mol Ther 16(10): 1737-44.

Johnston, L. C., X. Su, et al. (2008).
"Human interleukin-10 gene transfer is protective in a rat model of Parkinson's disease." Mol Ther 16(8): 1392-9.

Kells, A. P., P. Hadaczek, et al. (2009).
"Efficient gene therapy-based method for the delivery of therapeutics to primate cortex." Proc Natl Acad Sci U S A.

Kikuchi, T., R. Saito, et al. (2008).
"Convection-enhanced delivery of polyethylene glycol-coated liposomal doxorubicin: characterization and efficacy in rat intracranial glioma models." J Neurosurg 109(5): 867-73.

Krauze, M. T., S. R. Vandenberg, et al. (2008).
"Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective." Exp Neurol 210(2): 638-44.

Richardson, R. M., P. S. Larson, et al. (2008).
"Gene and cell delivery to the degenerated striatum: status of preclinical efforts in primate models." Neurosurgery 63(4): 629-442; dicussion 642-4.

Varenika, V., P. Dickinson, et al. (2008).
"Detection of infusate leakage in the brain using real-time imaging of convection-enhanced delivery." J Neurosurg 109(5): 874-80.

2007

Krauze, M. T., Noble, C. O., Kawaguchi, T., Drummond, D., Kirpotin, D. B., Yamashita, Y., Kullberg, E., Forsayeth, J., Park, J. W., and Bankiewicz, K. S., 2007.
Convection-enhanced delivery of nanoliposomal CPT-11 (irinotecan) and PEGylated liposomal doxorubicin (Doxil) in rodent intracranial brain tumor xenografts. Neuro Oncol 9, 393-403

Yamashita, Y., Krauze, M. T., Kawaguchi, T., Noble, C. O., Drummond, D. C., Park, J. W., and Bankiewicz, K. S., 2007.
Convection-enhanced delivery of a topoisomerase I inhibitor (nanoliposomal topotecan) and a topoisomerase II inhibitor (pegylated liposomal doxorubicin) in intracranial brain tumor xenografts. Neuro Oncol 9, 20-28

Krauze, M. T., Vandenberg, S. R., Yamashita, Y., Saito, R., Forsayeth, J., Noble, C., Park, J., and Bankiewicz, K. S., 2007.
Safety of real-time convection-enhanced delivery of liposomes to primate brain: A long-term retrospective. Exp Neurol

2006

Hadaczek, P., Yamashita, Y., Mirek, H., Tamas, L., Bohn, M. C., Noble, C., Park, J. W., and Bankiewicz, K., 2006.
The "perivascular pump" driven by arterial pulsation is a powerful mechanism for the distribution of therapeutic molecules within the brain. Mol Ther 14, 69-78

Hadaczek, P., Kohutnicka, M., Krauze, M. T., Bringas, J., Pivirotto, P., Cunningham, J., and Bankiewicz, K., 2006.
Convection-enhanced delivery of adeno-associated virus type 2 (AAV2) into the striatum and transport of AAV2 within monkey brain. Hum Gene Ther 17, 291-302

Noble, C. O., Krauze, M. T., Drummond, D. C., Yamashita, Y., Saito, R., Berger, M. S., Kirpotin, D. B., Bankiewicz, K. S., and Park, J. W., 2006.
Novel nanoliposomal CPT-11 infused by convection-enhanced delivery in intracranial tumors: pharmacology and efficacy. Cancer Res 66, 2801-2806

Saito, R., Krauze, M. T., Noble, C. O., Drummond, D. C., Kirpotin, D. B., Berger, M. S., Park, J. W., and Bankiewicz, K. S., 2006.
Convection-enhanced delivery of Ls-TPT enables an effective, continuous, low-dose chemotherapy against malignant glioma xenograft model. Neuro Oncol 8, 205-214

Sampson, J. H., Akabani, G., Friedman, A. H., Bigner, D., Kunwar, S., Berger, M. S., and Bankiewicz, K. S., 2006.
Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies. Neurosurg Focus 20, E14

Krauze, M. T., Forsayeth, J., Park, J. W., and Bankiewicz, K. S., 2006.
Real-time imaging and quantification of brain delivery of liposomes. Pharm Res 23, 2493-2504

Saito, R., Krauze, M. T., Noble, C. O., Tamas, M., Drummond, D. C., Kirpotin, D. B., Berger, M. S., Park, J. W., and Bankiewicz, K. S., 2006.
Tissue affinity of the infusate affects the distribution volume during convection-enhanced delivery into rodent brains: implications for local drug delivery. J Neurosci Methods 154, 225-232

Bankiewicz, K. S., Daadi, M., Pivirotto, P., Bringas, J., Sanftner, L., Cunningham, J., Forsayeth, J. R., and Eberling, J. L., 2006
Focal striatal dopamine may potentiate dyskinesias in parkinsonian monkeys. Exp Neurol 197, 363-372

Bankiewicz, K. S., Forsayeth, J., Eberling, J. L., Sanchez-Pernaute, R., Pivirotto, P., Bringas, J., Herscovitch, P., Carson, R. E., Eckelman, W., Reutter, B., and Cunningham, J., 2006.
Long-term clinical improvement in MPTP-lesioned primates after gene therapy with AAV-hAADC. Mol Ther 14, 564-570

Forsayeth, J. R., Eberling, J. L., Sanftner, L. M., Zhen, Z., Pivirotto, P., Bringas, J., Cunningham, J., and Bankiewicz, K. S., 2006.
A dose-ranging study of AAV-hAADC therapy in Parkinsonian monkeys. Mol Ther 14, 571-577

2005

Hadaczek, P., Mirek, H., Berger, M. S., and Bankiewicz, K., 2005.
Limited efficacy of gene transfer in herpes simplex virus-thymidine kinase/ganciclovir gene therapy for brain tumors. J Neurosurg 102, 328-335

Krauze, M. T., McKnight, T. R., Yamashita, Y., Bringas, J., Noble, C. O., Saito, R., Geletneky, K., Forsayeth, J., Berger, M. S., Jackson, P., Park, J. W., and Bankiewicz, K. S., 2005.
Real-time visualization and characterization of liposomal delivery into the monkey brain by magnetic resonance imaging. Brain Res Brain Res Protoc 16, 20-26

Krauze, M. T., Saito, R., Noble, C., Bringas, J., Forsayeth, J., McKnight, T. R., Park, J., and Bankiewicz, K. S., 2005.
Effects of the perivascular space on convection-enhanced delivery of liposomes in primate putamen. Exp Neurol 196, 104-111

Krauze, M. T., Saito, R., Noble, C., Tamas, M., Bringas, J., Park, J. W., Berger, M. S., and Bankiewicz, K., 2005.
Reflux-free cannula for convection-enhanced high-speed delivery of therapeutic agents. J Neurosurg 103, 923-929

Saito, R., Krauze, M. T., Bringas, J. R., Noble, C., McKnight, T. R., Jackson, P., Wendland, M. F., Mamot, C., Drummond, D. C., Kirpotin, D. B., Hong, K., Berger, M. S., Park, J. W., and Bankiewicz, K. S., 2005.
Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain. Exp Neurol 196, 381-389

Sanftner, L. M., Sommer, J. M., Suzuki, B. M., Smith, P. H., Vijay, S., Vargas, J. A., Forsayeth, J. R., Cunningham, J., Bankiewicz, K. S., Kao, H., Bernal, J., Pierce, G. F., and Johnson, K. W., 2005.
AAV2-mediated gene delivery to monkey putamen: evaluation of an infusion device and delivery parameters. Exp Neurol 194, 476-483

2004

Hadaczek, P., Mirek, H., Bringas, J., Cunningham, J., and Bankiewicz, K., 2004.
Basic fibroblast growth factor enhances transduction, distribution, and axonal transport of adeno-associated virus type 2 vector in rat brain. Hum Gene Ther 15, 469-479

Saito, R., Bringas, J., Mirek, H., Berger, M. S., and Bankiewicz, K. S., 2004.
Invasive phenotype observed in 1,3-bis(2-chloroethyl)-1-nitrosourea-resistant sublines of 9L rat glioma cells: a tumor model mimicking a recurrent malignant glioma. J Neurosurg 101, 826-831

Saito, R., Bringas, J. R., Panner, A., Tamas, M., Pieper, R. O., Berger, M. S., and Bankiewicz, K. S., 2004.
Convection-enhanced delivery of tumor necrosis factor-related apoptosis-inducing ligand with systemic administration of temozolomide prolongs survival in an intracranial glioblastoma xenograft model. Cancer Res 64, 6858-6862

Mamot, C., Nguyen, J. B., Pourdehnad, M., Hadaczek, P., Saito, R., Bringas, J. R., Drummond, D. C., Hong, K., Kirpotin, D. B., McKnight, T., Berger, M. S., Park, J. W., and Bankiewicz, K. S., 2004.
Extensive distribution of liposomes in rodent brains and brain tumors following convection-enhanced delivery. J Neurooncol 68, 1-9

Saito, R., Bringas, J. R., McKnight, T. R., Wendland, M. F., Mamot, C., Drummond, D. C., Kirpotin, D. B., Park, J. W., Berger, M. S., and Bankiewicz, K. S., 2004.
Distribution of liposomes into brain and rat brain tumor models by convection-enhanced delivery monitored with magnetic resonance imaging. Cancer Res 64, 2572-2579

2003

D'Costa, J., Harvey-White, J., Qasba, P., Limaye, A., Kaneski, C. R., Davis-Warren, A., Brady, R. O., Bankiewicz, K. S., Major, E. O., and Arya, S. K., 2003.
HIV-2 derived lentiviral vectors: gene transfer in Parkinson's and Fabry disease models in vitro. J Med Virol 71, 173-182

Eberling, J. L., Cunningham, J., Pivirotto, P., Bringas, J., Daadi, M. M., and Bankiewicz, K. S., 2003.
In vivo PET imaging of gene expression in Parkinsonian monkeys. Mol Ther 8, 873-875

Emborg, M. E., Tetrud, J. W., Moirano, J., McLaughlin, W. W., and Bankiewicz, K. S., 2003.
Rest tremor in rhesus monkeys with MPTP-induced parkinsonism. Front Biosci 8, a148-154

Oiwa, Y., Eberling, J. L., Nagy, D., Pivirotto, P., Emborg, M. E., and Bankiewicz, K. S., 2003.
Overlesioned hemiparkinsonian non human primate model: correlation between clinical, neurochemical and histochemical changes. Front Biosci 8, a155-166

Oiwa, Y., Sanchez-Pernaute, R., Harvey-White, J., and Bankiewicz, K. S., 2003.
Progressive and extensive dopaminergic degeneration induced by convection-enhanced delivery of 6-hydroxydopamine into the rat striatum: a novel rodent model of Parkinson disease. J Neurosurg 98, 136-144

Goldstein, D. S., Li, S. T., Holmes, C., and Bankiewicz, K., 2003.
Sympathetic innervation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine primate model of Parkinson's disease. J Pharmacol Exp Ther 306, 855-860

2002

Kim, J. H., Auerbach, J. M., Rodriguez-Gomez, J. A., Velasco, I., Gavin, D., Lumelsky, N., Lee, S. H., Nguyen, J., Sanchez-Pernaute, R., Bankiewicz, K., and McKay, R., 2002.
Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease. Nature 418, 50-56

2001

Hamilton, J. F., Morrison, P. F., Chen, M. Y., Harvey-White, J., Pernaute, R. S., Phillips, H., Oldfield, E., and Bankiewicz, K. S., 2001.
Heparin coinfusion during convection-enhanced delivery (CED) increases the distribution of the glial-derived neurotrophic factor (GDNF) ligand family in rat striatum and enhances the pharmacological activity of neurturin. Exp Neurol 168, 155-161

Nguyen, J. B., Sanchez-Pernaute, R., Cunningham, J., and Bankiewicz, K. S., 2001.
Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain. Neuroreport 12, 1961-1964

Sanchez-Pernaute, R., Harvey-White, J., Cunningham, J., and Bankiewicz, K. S., 2001.
Functional effect of adeno-associated virus mediated gene transfer of aromatic L-amino acid decarboxylase into the striatum of 6-OHDA-lesioned rats. Mol Ther 4, 324-330

Sanchez-Pernaute, R., Studer, L., Bankiewicz, K. S., Major, E. O., and McKay, R. D., 2001.
In vitro generation and transplantation of precursor-derived human dopamine neurons. J Neurosci Res 65, 284-288

2000

Bankiewicz, K. S., Bringas, J., Pivirotto, P., Kutzscher, E., Nagy, D., and Emborg, M. E., 2000.
Technique for bilateral intracranial implantation of cells in monkeys using an automated delivery system. Cell Transplant 9, 595-607

Cunningham, J., Oiwa, Y., Nagy, D., Podsakoff, G., Colosi, P., and Bankiewicz, K. S., 2000.
Distribution of AAV-TK following intracranial convection-enhanced delivery into rats. Cell Transplant 9, 585-594

Qureshi, N. H., Bankiewicz, K. S., Louis, D. N., Hochberg, F. H., Chiocca, E. A., and Harsh, G. R. t., 2000.
Multicolumn infusion of gene therapy cells into human brain tumors: technical report. Neurosurgery 46, 663-668; discussion 668-669

Bankiewicz, K. S., Eberling, J. L., Kohutnicka, M., Jagust, W., Pivirotto, P., Bringas, J., Cunningham, J., Budinger, T. F., and Harvey-White, J., 2000.
Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. Exp Neurol 164, 2-14

Eberling, J. L., Pivirotto, P., Bringas, J., and Bankiewicz, K. S., 2000.
Tremor is associated with PET measures of nigrostriatal dopamine function in MPTP-lesioned monkeys. Exp Neurol 165, 342-346