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You searched for +publisher:"University of North Carolina" +contributor:("McCown, Thomas"). One record found.

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University of North Carolina

1. Foti, Stacey. Novel AAV-mediated Therapeutic Strategies for Epilepsy.

Degree: 2008, University of North Carolina

Epilepsy afflicts 2.1 million people in the United States, and many patients develop drug resistant seizures. For these patients, gene therapy may be an attractive treatment option. Recent studies have shown that viral vector-mediated expression of neuropeptides such as galanin and neuropeptide Y (NPY) can attenuate seizure sensitivity and prevent seizure-induced cell death in the brain. NPY13-36 is a C-terminal peptide fragment of NPY that activates the NPY-Y2 receptor, thought to mediate the anti-seizure activity. Therefore we investigated if recombinant adeno-associated virus (AAV)-mediated expression and constitutive secretion of NPY or NPY13-36 could alter limbic seizure sensitivity. We found that AAV-mediated delivery of both NPY and NPY13-36 attenuates limbic seizures, and provides a vector technology platform for delivering therapeutic peptide fragments with increased receptor selectivity. To further explore the potential of this platform, we utilized a strategic approach to deliver multiple neuropeptides simultaneously. To achieve this, we used a proteolytic strategy such that our vectors contained a single promoter driving expression of a cleavable chimeric fusion protein of galanin and NPY13-36. The chimeric fusion protein contained a linker sequence capable of being cleaved by the intracellular protease furin, and also contained a fibronectin constitutive secretion signal (FIB) sequence. We first characterized several constructs in vitro, and determined that 1) a single FIB sequence was sufficient to cause secretion of both proteins, 2) the proteins were cleaved from one another regardless of position relative to the cleavage sequence, 3) cleavage efficiency of secreted proteins was 100%, 4) if the cleavage sequence was absent, uncleaved fusion protein was secreted into the medium. We then tested these constructs in a limbic seizure model, and showed that all of our vectors were capable of attenuating limbic seizure sensitivity. However, no additional efficacy was observed with the vector delivering both galanin and NPY13-36. Surprisingly, the level of attenuation was less than with previously published single peptide vectors, suggesting reduced translation efficiency. This body of work describes a gene therapy vector technology platform to express and constitutively secrete single and multiple proteins from transduced cells, and to deliver peptide fragments that are capable of selective receptor targeting. Advisors/Committee Members: Foti, Stacey, McCown, Thomas, Samulski, Richard, Deshmukh, Mohanish, Kafri, Tal, Lund, Pauline Kay.

Subjects/Keywords: School of Medicine; UNC Neuroscience Center; Neuroscience Curriculum

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APA (6th Edition):

Foti, S. (2008). Novel AAV-mediated Therapeutic Strategies for Epilepsy. (Thesis). University of North Carolina. Retrieved from https://cdr.lib.unc.edu/record/uuid:a332c4e2-79fa-4b41-97b5-d1786e2656b8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Foti, Stacey. “Novel AAV-mediated Therapeutic Strategies for Epilepsy.” 2008. Thesis, University of North Carolina. Accessed October 31, 2020. https://cdr.lib.unc.edu/record/uuid:a332c4e2-79fa-4b41-97b5-d1786e2656b8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Foti, Stacey. “Novel AAV-mediated Therapeutic Strategies for Epilepsy.” 2008. Web. 31 Oct 2020.

Vancouver:

Foti S. Novel AAV-mediated Therapeutic Strategies for Epilepsy. [Internet] [Thesis]. University of North Carolina; 2008. [cited 2020 Oct 31]. Available from: https://cdr.lib.unc.edu/record/uuid:a332c4e2-79fa-4b41-97b5-d1786e2656b8.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Foti S. Novel AAV-mediated Therapeutic Strategies for Epilepsy. [Thesis]. University of North Carolina; 2008. Available from: https://cdr.lib.unc.edu/record/uuid:a332c4e2-79fa-4b41-97b5-d1786e2656b8

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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