CURRICULUM VITAE

Andrew Freese, M.D., Ph.D.

Personal:Born: Boston, MA on July 4, 1959Work Address: University of Minnesota, Department of Neurosurgery, D429 Mayo Memorial

Building, 420 Delaware Street, S.E., Minneapolis, MN 55455, tel: 612.624.2471Marital Status: Married with four children

Present Positions:Professor and Vice Chairman, Department of Neurosurgery and Director of Spinal

Neurosurgery, University of Minnesota Medical School; Professor, Institute of Human Genetics and Dept. of Neuroscience, University of MinnesotaExecutive Director, The CNS Gene Therapy Consortium, 1803 Pine Street, Suite 1,

Philadelphia, PA 19103;Senior Research Fellow, Cell and Gene Therapy Center, Robert Wood Johnson Medical

School, Camden, N.J.;Co-Founder and Scientific Director, BioSpinex, Inc., Gilbertsville, PA 19525;Member, Scientific Advisory Board, IntraVantage, Inc., Plymouth, MN 55441

Education:Neurosurgery Residency, 1991-1997: University of Pennsylvania, Philadelphia, PA Surgical Internship, 1990-1991: University of Pennsylvania, Philadelphia, PAPh.D., 1992: Massachusetts Institute of Technology, Cambridge, MA; Division of Health

Sciences and Technology (HST), Program in Applied Biology in MedicineM.D., 1990: Harvard Medical School, Boston, MA; Health Sciences and Technology with

Honors ThesisB.A., 1981: Harvard University, Cambridge, MA, Biochemistry (Magna Cum Laude with High

Honors Thesis).

Professional Associations:American Medical Association (AMA); American Association for the Advancement of Science (AAAS); Sigma Xi Academic Honorary Society (MIT Chapter); Society for Neuroscience; International Brain Research Organization; International Society for Neurochemistry; Controlled Release Society; New York Academy of Sciences; Minnesota Medical Association; Minnesota Neurosurgical Society; Pennsylvania Neurosurgical Society; American Association of Neurological Surgeons; Congress of Neurological Surgeons; American Heart Association, Council on Basic Science and Council on Stroke; American Epilepsy Society; The CNS Gene Therapy Consortium; American Society for Gene Therapy; North American Spine Society

Licensure and Accreditation:State of Minnesota M.D. Licence (active); State of Pennsylvania M.D. License (inactive);Licensure and Accreditation, continued:United States Drug Enforcement Agency (DEA) Controlled Substances License;

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Diplomate, National Board of Medical Examiners (USA);Board Certification, American Board of Neurological Surgeons

Honors and Awards:Harvard University Scholarships 1978-1981; Dean's List 1978-1981; High Honors Thesis (Biochemistry), Harvard University, 1981; Sigma Xi (MIT); Medical Scientist Training Program M.D., Ph.D. Fellowship, 1986-1990; M.D. Honors Thesis, Harvard Medical School, 1990; Nemir Research Foundation Award, 1993; DeHillebranth Foundation Research Award, 1994; American Men and Women of Science, 1994; Who's Who in Healthcare and Medicine, 1997-2004; Who's Who in Science and Engineering, 1998-2004; Who's Who in America, 1998-2004; Strawbridge Research Fund Award, 1999-2000; Physician/Scientist of the Year Award, Canavan Foundation, Illinois, 2004

Additional Skills and Previous Work Experience:2003-2004: Professor of Neurosurgery, Drexel Univ. College of Medicine, Philadelphia, PA2003-2004: Director of the Graduate Spine Center, Graduate Hospital of the Drexel University

College of Medicine; Philadelphia, PA2000-2003: Vice Chairman of Neurosurgery, Thomas Jefferson University, Philadelphia, PA1997-2003: Director of Neurosurgery Research, Thomas Jefferson University, Philadelphia, PA1997-2003: Associate Professor of Neurosurgery, Thomas Jefferson University, Philadelphia, PA 1997-2002: Associate Director, CNS Gene Therapy Center, Thomas Jefferson University,

Philadelphia, PA1997-2003: Director of Division of Molecular Neurosurgery, Thomas Jefferson University,

Philadelphia,PA1999-2003: Clinical Mentor, Rothman Institute and Neurosurgery Spine Fellowship

Programs, Thomas Jefferson University1997-1999: Co-Founder and Treasurer, Medagen, Inc., 400 Hamilton Ave., Palo Alto, CA

94301 – restructured as Neurologix, Inc., New York, NY 1997: Visiting Professor, Division of Functional Neurosurgery; University of Toronto.1996-1997: Clinical Instructor and Chief Resident, Dept. Neurosurgery, University of

Pennsylvania, Philadelphia, PA.1994-1997: Director, Laboratory of Molecular Neurosurgery, The Graduate Hospital of the

University of Pennsylvania, Philadelphia, PA1994-1997: Member, Institute for Human Gene Therapy, University of Pennsylvania.1995-1997: Member, Wistar Institute Glioma Group1995: Spinal Surgery and Instrumentation Elective Fellowship, Hospital of the University of

Pennsylvania, Philadelphia, PA (6 months).1994-1995: Visiting Scientist, Wistar Institute, Philadelphia, PA.1993-1995: Scientific Consultant, Polykinetix, Inc., New York, NY.1993: Surgical Epilepsy Fellowship, Graduate Hospital/University of Pennsylvania

Comprehensive Epilepsy Program, Philadelphia, PA (6 months).1991-1993: Junior Resident, Division of Neurosurgery, Hospital of the University of

Pennsylvania, Philadelphia, PA.1990-1991: Surgical Intern, Department of Surgery, Hospital of the University of

Pennsylvania, Philadelphia, PA.Additional Skills and Previous Work Experience, continued:

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1989-1990: Scientific Director, Neurel, Inc., Boston, MA.1987-1989: President and Co-Founder, Neurel, Inc., Boston, MA.1985-1986: Teaching Fellow for Basic Neuroscience Course, Harvard Medical School, Boston,

MA.1983: Research Assistant, Laboratory of Molecular Biology, NINCDS, NIH, Bethesda, MD.1981: Summer Research Assistant, Dept. of Medicine, Mass. General Hospital, Boston, MA.1980: Staff Assistant, National Academy of Sciences, Washington, D.C. 1979: Research Assistant, Laboratory of Developmental and Metabolic Neurology, NINCDS,

NIH, Bethesda, MD. Cervical Spine Think Tank, Synthes Spine, Sept, 2003 Think Tank for Biological Approaches to Spinal Disorders, Medtronic/Sofamor Danek

May, 2001 and May, 2002 NIH Grant Review Committee, NINDS, RFA-NS-02-007 for Gene Therapy of

Neurological Disorders; March, 2002 Peer Review Panel on Department of Defense Congressionally Directed Medical Research

Program on Defense and Veterans Head Injury Program (USAMRMC), October, 2000 Grant Reviewer, American Institute of Biological Sciences, July, 2000 Peer Review Panel on Neurotoxin Exposure for US Army Medical Research and Material

Command (USAMRMC), September, 1998 Developed Residency brochure and Website for Department of Neurosurgery, Thomas

Jefferson University Invited Guest Editor for Experimental Neurology, March, 1997 issue Organized International Conference on Gene Therapy for CNS Disorders, sponsored by the University of Pennsylvania, held June 8-10, 1995, Philadelphia, PA Co-Founder and Executive Director of The Parkinson's Disease Gene Therapy Consortium,

an international organization of approximately 60 scientists and clinicians dedicated to evaluating gene therapy and related approaches to Parkinson's Disease--first meeting held April 11- 13, 1996; renamed The CNS Gene Therapy Consortium

Ad-hoc Reviewer: Proceedings of the National Academy of Sciences (USA), Journal of Controlled Release, Brain Research, Biomaterials, Human Gene Therapy, Neurosurgery, and Experimental Neurology

Referee for Marsden Fund; New Zealand Foundation for Research, Science and Technology

Board of Directors, Canavan Disease Research Foundation Fluent in French and German

Established Collaborative Research Programs: Performed first AAV (adeno-associated virus) gene transfer into the human brain in a FDA

approved clinical trial. Co-established world’s first clinical (FDA-approved) trial for gene therapy of a non-

malignant CNS disorder, Canavan Disease, at Th. Jefferson Univ., using liposome vectors. Gene therapy approaches to Parkinson's Disease, introducing genes encoding

neurotransmitter biosynthetic enzymes and neurotrophic factors into the CNS. Development of novel instrumentation and navigation systems for spinal surgery Gene therapy for pituitary (lactotroph, gonadotroph and somatotroph) adenomas.

Established Collaborative Research Programs, continued:3

Gene therapy of neurometabolic diseases (including Canavan Disease and phenylketonuria) Analysis of polymeric and liposomal drug delivery devices for application to Neurosurgical

and Spine disorders. Clinical and radiological evaluation of spinal instrumentation and fusion procedures.

Grants:1) Development of Gene and Cellular Therapy for Spine Disorders. Synthes Spine, Inc.,

Direct Costs: $85,000 (Principal Investigator, November, 2004-October, 2004)2) Development of Gene and Cellular Therapy for Spine Disorders. Synthes Spine, Inc.,

Direct Costs: $65,000 (Principal Investigator, October, 2003-October, 2004)3) Evaluation of Cervical Spinal Instrumentation Systems. Medtronic Sofamor Danek, Inc.,

Direct Costs: $55,000 (Principal Investigator, 2001-2003)4) Aspartoacylase Gene Transfer in brain/Canavan Disease, RO1 NS42120-1, NIH/NINDS

Pilot Clinical Grant, Total Costs: $583,258 (principal clinical investigator, 2001-2003)5) Towards Gene Therapy of Parkinson's Disease. NIH-RO1 NS 39144 Direct Costs:

$756,000 (co-investigator, 1999-2002)6) Development of gene therapy approaches to Parkinson's Disease. Progen, Inc. Direct

Costs: $80,000 (Principal Investigator, 2000)7) Gene Therapy of Canavan Disease. Strawbridge Research Fund, Direct Costs: $150,000

(Principal Investigator, 1999-2000)

Publications:

Original Articles, Reviews, and Letters:

Freese, A., Brady, R.O., Gal, A.E. (1980): A ß-Glucosidase in Feline Kidney that Hydrolyzes Amygdalin (Laetrile). Archives of Biochemistry and Biophysics, 201(2): 363-368.

Liscovitch, M., Freese, A., Blusztain, J.K., Wurtman, R.J. (1985): High Performance Liquid Chromatography of Water-Soluble Choline Metabolites. Analytical Biochemistry, 151:182-187.

Liscovitch, M., Freese, A., Blusztajn, J.K., Wurtman, R.J. (1986): Phosphatidylcholine Biosynthesis in the Neuroblastoma-Glioma Hybrid Cell Line NG108-15: Stimulation by Phorbol Esters. Journal of Neurochemistry, 47(6): 1936-1941.

Blusztajn, J.K., Liscovitch, M., Freese, A., Wurtman, R.J. (1987): Stimulation of Choline Release from NG108-15 Cells by 12-0-tetradecanoylphorbol 13-acetate. Biochemical Journal, 241:81-86.

Freese, A., Swartz, K.J., During, M.J. (1988): Branched Chain Amino Acids in Amyotrophic Lateral Sclerosis. The Lancet, 8612:680-682.

During, M.J., Freese, A. (1988): L-Tryptophan, a Natural but not Necessarily Safe Antidepressant. Australian and New Zealand Journal of Psychiatry, 22:339.

Publications, continued:

Original Articles, Reviews, and Letters, continued:

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Freese, A. (1988): Excitotoxic Models of Huntington's Disease. Proceedings of the MIT Health Sciences and Technology Forum, 2:53-59.

Freese, A., Sabel, B.A., Saltzman, W.M., During, M.J., and Langer, R. (1989): Controlled Release of Catecholamines from a Polymeric Brain Implant: In Vitro Characterization. Experimental Neurology, 103:234-238.

During, M.J., Freese, A, Sabel, B.A., Deutch, A., Roth, R.E., Langer, R. (1989): Controlled Release of Catecholamines from a Polymeric Brain Implant: In Vivo Characterization. Annals of Neurology, 25:351-356.

During, M.J., Heyes, M.P., Freese, A., Markey, S.P., Martin, J.B., Roth, R.H. (1989): Quinolinic Acid Concentrations in Striatal Extracellular Fluid Reach Potentially Neurotoxic Levels Following Systemic L-Tryptophan Loading. Brain Research, 476:384-387.

During, M.J., Freese, A., Heyes, M.P., Swartz, K.J., Markey, S., Roth, R.H., Martin, J.B (1989): Neuroactive Metabolites of L-Tryptophan, Serotonin and Quinolinic Acid, in Striatal Extracellular Fluid: Effect of Tryptophan Loading. FEBS Letters, 247:438-444.

Geller, A.I., Freese, A. (1989): An HSV- 1 Vector System to Transfer Genes into Neurons in the Adult Rat Brain. Experimental Medicine,7:81-93.

Freese, A., Swartz, K.J., During, M.J., Martin, J.B. (1990): Kynurenine Metabolites of Tryptophan: Implications for Neurological Disease. Neurology, 40:691-695.

Geller, A.I., Freese, A. (1990): Transfection of Cultured Central Nervous System Neurons with a Defective HSV-1 Vector which Stably Expresses ß-Galactosidase. Proceedings of the National Academy of Sciences, USA, 87:1149-1153.

Freese, A., Neve, R., Geller, A.I. (1990): HSV-1 Vector Mediated Neuronal Gene Delivery: Strategies for Molecular Neuroscience and Neurology. Biochemical Pharmacology, 40:2189-2199.

Freese, A., DiFiglia, M., Beal, M.F., Martin, J.B. (1990): Characterization and Mechanism of Glutamate Toxicity in Primary Striatal Cultures. Brain Research, 521:254-264.

Koroshetz, W.J., Freese, A., DiFiglia, M. (1990): Correlation between Excitatory Amino Acid Induced Current Responses and Excitotoxicity in Striatal Cultures. Brain Research, 521:265-272.

Freese, A., Finn, S.F., During, M.J. (1990): Eosinophilia Myalgia Syndrome, Tryptophan and Quinolinic Acid. Annals of Internal Medicine, 112:795.

Sabel, B.A., Dominiak, P., Hauser, W., During, M.J., Freese, A. (1990): Extended Levodopa Release from a Subcutaneously Implanted Polymer Matrix in Rats. Annals of Neurology, 28:714-717.

Sabel, B.A., Dominiak, P., Hauser, W., During, M.J., Freese, A. (1990): Levodopa Delivery from a Controlled-Release Polymer Matrix: Delivery of More than 600 Days and 225 Days of Elevated Plasma Levels after Subcutaneous Implantation in Rats. The Journal of Pharmacology and Experimental Therapeutics, 255:914-922.

Swartz, K.J., During, M.J., Freese, A., Beal, M.F. (1990): Cerebral Synthesis and Release of Kynurenic Acid: An Endogenous Antagonist of Excitatory Amino Acid Receptors. The Journal of Neuroscience, 10:2965-2973.

Publications, continued:

Original Articles, Reviews, and letters, continued:5

During, M.J., Heyes, M.P., Freese, A., Swartz, K.J., Matson, W.R., Markey, S.P., Martin, J.B., Roth, R.H. (1991): Indolic and Kynurenine Pathway Metabolites of Tryptophan in Rat Brain: Effect of Precursor Availability on In Vivo Release. Advances in Experimental and Medical Biology, 294:535-539.

Freese, A., Geller, A.I. (1991): Infection of Cultured Striatal Neurons with a Defective HSV-1 Vector: Implications for Gene Therapy. Nucleic Acids Research, 19:7219-7223.

During, M.J., Freese, A., Deutch, A.Y., Kibat, P., Sabel, B.A., Langer, R., Roth, R.H. (1992): Biochemical and Behavioral Recovery in a Rodent Model of Parkinson's Disease following Stereotactic Implantation of Dopamine-containing Liposomes. Experimental Neurology, 115:193-199.

Freese, A., Finklestein, S., and DiFiglia, M. (1992): Basic Fibroblast Growth Factor Protects Striatal Neurons In Vitro from NMDA Receptor Mediated Excitotoxicity. Brain Research, 575:351-355.

Geller, A.I., During, M.J., Haycock, J.W., Freese, A., Neve, R. (1993): Long-term increases in Neurotransmitter Release from Neuronal Cells Expressing a Constitutively Active Adenylate Cyclase from a Herpes Simplex Virus 'I'ype I Vector. Proceedings of the National Academy of Sciences, USA, 90:7603-7607.

Jans, A., Galetta, S.L., Freese, A., Raps, E.C., Curtis, M., Grossman, R.I., Gomori, J.M., Duhaime, A.C. (1993): Superficial Siderosis of the Central Nervous System: MRI and Pathologic Correlation. Journal of Neurosurgery, 79:756-760.

Freese, A., O'Rourke, D., Judy, K., O'Connor, M.J. (1994): Application of 5-Bromodeoxyuridine to Neurosurgery, Journal of Neuro-Oncology, 20:81-95.

Geller, A.I., During, M.J., Oh, Y.J., Freese, A., O'Malley, K. (1995): A HSV-1 Vector Expressing Tyrosine Hydroxylase Causes Production and Release of L-DOPA and Dopamine from Cultured Rat Striatal Neurons. Journal of Neurochemistry, 64:487-496.

O'Connor, W.M., Masukawa, L.M., Freese, A., Sperling, M.R., French, J.A., O'Connor, M.J. (1996): Hippocampal Cell Distributions in Temporal Lobe Epilepsy: A Comparison between Patients With and Without an Early Risk Factor, Epilepsia, 37(5): 440-449.

Freese, A., During, M.J., Davidson, B., Kaplitt, M.G., Flamm, E.S., Gennarelli, T.A., Snyder, P.J. (1996): Modulation of Prolactin Secretion from Human Lactotroph Adenoma Cells with an Adenovirus Vector containing the Tyrosine Hydroxylase Gene, Journal of Clinical Endocrinology and Metabolism, 81(6):2401-2404.

Freese, A., Stern, M., Kaplitt, M.G., O'Connor, W.M., Abbey, M.V., O'Connor, M.J., During, M.J. (1996): Prospects for Gene Therapy in Parkinson's Disease, Movement Disorders, 11(5):469-488.

Stern, M.B., Freese, A. (1996): Gene Therapies and Parkinson's Disease. Parkinson Report, 17(2):13-14.

Schnee, C.L., Freese, A., Ansell, L.V. (1997): Outcome Analysis of Adults with Spondylolisthesis Treated with Posterolateral Fusion and Transpedicular Screw Fixation. Journal of Neurosurgery, 86:56-63.

Publications, continued:

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Original Articles, Reviews, and letters, continued:Dibbern, D.A., Loevner, L.A., Lexa, F.J., Lieberman, A.P., Salhany, K.E., Freese, A.,

Marcotte, P. (1997): Thoracic Cord Compression Due to Extramedullary Hematopoeisis in Myelodysplastic Syndrome: Findings on MRI Examination. American Journal of Neuroradiology, 18:363-366.

Stern, M.B., Freese, A. (1997): Parkinson's Disease: The Case for Novel Treatment Strategies. Experimental Neurology, 144:2-4.

Freese, A., During, M.J., O'Connor, W.M., Langer, D., O'Connor, M.J., Kaplitt, M.G. (1997): Direct Gene Transfer into Human Epileptogenic Hippocampus tissue with an Adeno-associated Virus Vector, Epilepsia, 38(7): 759-766.

Schnee, C.L., Freese, A., Weil, R.J., Marcotte, P.J. (1997): Anterior Cervical Reconstruction using Iliac Crest Autograft: Harvest Complications and Graft Outcomes, Spine, 22(19):2222-2227.

O'Connor, W.M., Davidson, B., Kaplitt, M.G., O'Connor, M.J., Langer, D., During, M.J., Freese, A. (1997): Adenovirus Vector Mediated Gene Transfer into Human Epileptogenic Brain Slices: Prospects for Gene Therapy in Epilepsy, Experimental Neurology, 148:167-178.

During, M.J., Samulski, R.J., Elsworth, J.D., Kaplitt, M.G., Leone, P., Xiao, X., Li, J., Freese, A., Roth, R.H., Sladek, J.R., O'Malley, K.L., Redmond, D.E. (1998): In Vivo Expression of Therapeutic Human Genes for Dopamine Production in the Caudates of MPTP-Treated Monkeys Using an AAV Vector, Gene Therapy, 5: 820-827.

Freese, A. (1999): Restorative Gene Therapy Approaches to Parkinson's Disease, Medical Clinics of North America, 83:537-48.

Freese, A., Simeone, F.A. (1999): Treatment of Neurosurgical Disease in the New Millenium, Ophthalmology Clinics of North America, 12(4):533-537.

Leone, P., McPhee, S.W., Janson, C.G., Liu, C., Silver, D., Davidson, B.L., Freese, A., During, M.J. (2000): Multi-site Partitioned Delivery of Human Tyrosine Hydroxylase Gene with Phenotypic Recovery in Parkinsonian rats, Neuroreport, 11(6):1145-51.

Leone, P., Janson, C.G., Bilianuk L., Wang, J., Sorgi, F., McPhee, S.W., Haung, L., Matalon, R., Kaul, R., Freese, A., Young, D., Xu, R., Mee, E., During, M.J. (2000): Apartoacylase Gene Transfer to the Mammalian Nervous System with Therapeutic Implications for Canavan Disease, Annals of Neurology, 48:27-38.

Janson, C.G., McPhee, S., Leone, P., Freese, A., During, M.J. (2001): Recombinant Viral-Based Gene Transfer to the Mammalian CNS for Functional Genomic Studies, Trends in Neuroscience.

Janson, C.G., McPhee, S., Bilaniuk, L., Haselgrove, J., Testaiuti, M., Freese, A., Wang, D-J., Shera, D., Hurh, P., Rupin, J., Saslow, E., Goldfarb, O., Goldberg, M., Larijani, G., Sharrar, W., Liouterman, L., Camp, A., Kolodny, E., Samulski, R.J., Leone, P. (2002): Gene Therapy of Canavan Disease: AAV-2 Vector for Neurosurgical Delivery of Aspartoacylase Gene (ASPA) to the Human Brain, Human Gene Therapy, 13:1391-1412.

Janson C.G., Leone, P., Freese, A. (2002): Parkinson’s Disease: Molecular Pathology, Science and Medicine, 8:328-337.

Janson C.G., Leone, P., Freese, A. (2003): Parkinson’s Disease: Cellular Basis of Medical Treatment, Science and Medicine, 9:24-35.

Publications, continued:

Original Articles, Reviews, and letters, continued:7

Janson C.G., Leone, P., Freese, A. (2003): Parkinson’s Disease: Surgical and Emerging Therapies, Science and Medicine, 9:82-95

McPhee, S., Francis, J., Janson, C.G., Serikawa, T., Hyland, K., Ong, E., Raghavan, S., Young, D., During, M.J., Freese, A. (2004): Effects of AAV-2 mediated aspartoacylase gene transfer in the tremor rat model of Canavan Disease, Brain Research, in press.

Leone, P., McPhee, S., Janson, C.G., Bilaniuk, L., Freese, A., Samulski, R.J. (2004): AAV vector delivery of the aspartoacylase gene in human brain, submitted.

Freese, A., (2004): Outcome evaluation of patients treated with posterior cervical decompression and instrumented fusion, in preparation.

Freese, A., Anderson, D.G., Weitzel, P.(2004): Evaluation of 114 patients with posterior cervical foraminotomies for cervical radiculopathy: relevance of preoperative axial neck pain, submitted

Abstracts:

Liscovitch, M., Freese, A., Blusztajn, J.K., Wurtman, R.J. (1985): High Performance Liquid Chromatography of Water-Soluble Choline Metabolites. Transactions of the American Society of Neurochemistry, 16(l): 61.

Liscovitch, M., Freese, A., Blusztajn, J.K., Wurtman, R.J. (1985): Phorbol Esters Stimulate Phosphatidylcholine Metabolism in NG108-15 Cells. Proceedings 15 th Annual Meeting, Society for Neuroscience, 11:118.5

Sabel, B.A., Freese, A., Saltzman, M., Langer, R. (1988): Long-term Controlled Release of L-DOPA and Dopamine from a Biocompatible Polymer Matrix System: In Vitro Characterization. Proceedings of the 9 th International Symposium on Parkinson's Disease.

During, M.J., Freese, A., Sabel, B.A., Deutch, A.Y., Langer, R., Roth, R.H. (1988): Controlled In Vivo Release of Dopamine from a Polymeric Brain Implant. Proceedings of the 9 th International Symposium on Parkinson's Disease .

Saltzman, W.M., Freese, A., Langer, R. (1988): Design and Testing of Polymeric Brain Implants for the Long-term Release of Dopamine and L-DOPA. Annual Meeting of the American Institute of Chemical Engineers.

Sabel, B.A., Freese, A., During, M.J., Saltzman, M., Langer, R. (1988): Polymer Brain Implants for Controlled Release of Dopamine: In Vitro and In Vivo Observations. Proceedings 18 th Annual Meeting, Society for Neuroscience , 14:308.9.

Sabel, B.A., Freese, A., During, M.J., Saltzman, M., Langer, R. (1988) Controlled Release of Dopamine from a Polymeric Brain Implant: In Vitro and In Vivo Observations. 17 th Proceedings of the International Society for Developmental Neuroscience.

Freese, A., DiFiglia, M., Beal, M.F., Martin, J.B. (1988): Characterization and Mechanism of Glutamate Neurotoxicity in Primary Striatal Cultures. Proceedings 18 th Annual Meeting, Society for Neuroscience, 14:169. 10.

During, M.J., Freese, A., Heyes, K.J., Swartz, K.J., Markey, S.P., Martin, J.B., Roth, R. (1988): Potential Neurotoxicity of Tryptophan: Striatal Quinolinic Acid Monitored by Microdialysis. Proceedings 18 th Annual Meeting, Society for Neuroscience , 14:290.14.

Publications, continued:

Abstracts, continued:

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Geller, A.I., Freese, A., Gusella, J.F., Breakefield, X.O. (1988): Tranfection of Neurons with a Defective HSV-1 Vector and Expression of ß-Galactosidase. Proceedings 18 th Annual Meeting, Society for Neuroscience, 14:254.11.

Koroshetz, W.J., Freese, A., DiFiglia, M., Corey, D.P. (1988): Correlation between Excitatory Amino Acid Induced Electrophysiological Responses and Neurotoxicity. Proceedings 18 th Annual Meeting, Society for Neuroscience , 14:169.9.

Freese, A., During, M.J. (1988): Drug Delivery for Neurological Disorders. Annual Conference for University/Incubator Spin-Off Companies, Technology Transfer Conferences, Boston, May 31-June 1.

Freese, A. (1988): Characterization and Mechanism of Glutamate Neurotoxicity in Primary Striatal Cultures. 2 nd Annual Health Sciences and Technology Forum , Massachusetts Institute of Technology.

Geller, A.I., Freese, A., Gusella, J.F., Breakefield, X.O. (1988): Tranfection of Neurons with HSV-1 Vectors: Implications for Studies on Aging. Annual Conference of the American Society for Aging Research, June 19-21.

Geller, A.I., Freese, A., Sabel, B.A. (1989): Modification of the Rat Nigrostriatal System by Intracerebral Injection of Defective HSV-1 Virus Vectors. Symposium on Parkinson's Disease and Other Basal Ganglia Disorders, Bad Kissingen, April 23-25.

Sabel, B.A., Martin, C., Waldmann, C., Freese, A., Geller, A.I. (1989): Gene Transfer into Neurons of the Adult Rat Brain. Proceedings 19 th Annual Meeting, Society for Neuroscience, 15:8:4.

Freese, A Acid Levels and Neurochemical Markers of Toxicity: Effects of Acute vs. Chronic Tryptopha., Swartz, K.J., During, M.J., Heyes, M.P., Beal, M.F., Martin, J.B. (1989): Regional Brain Quinolinic n Feeding. Proceedings 19 th Annual Meeting, Society for Neuroscience, 15:306:3.

Freese, A Acid Levels and Neurochemical Markers of Toxicity: Effects of Acute vs. Chronic Tryptopha., Swartz, K.J., During, M.J., Heyes, M.P., Beal, M.F., Martin, J.B. (1989): Regional Brain Quinolinic n Feeding. Proceedings 19 th Annual Meeting, Society for Neuroscience, 15:306:3.

During, M.J., Heyes, M.P., Freese, A., Swartz, K.J., Matson, W.R., Markey, S.P., Martin, J.B., Roth, R.H. (1989): Indoleamine and Kynurenine Pathway Metabolites ofTryptophan in Rat Brain. International Study Group for Tryptophan Research, p. 27.

Sabel, B.A., Freese, A., Geller, A. (1989): Transfer of a Recombinant Lac-Z Vector into Neurons of the Adult Rat Brain: Long-term Expression without Cell Death. Annual Meeting of the European Neuroscience Association.

Freese, A., Swartz, K.J. (1989): CNS Kynurenine Metabolites: Endogenous Agonists and Antagonists of Glutamate Receptors. 3 rd Annual Health Sciences and Technology Forum, Massachusetts Institute of Technology.

Geller, A.I., Neve, K., Freese, A., During, M.J., Neve, R. (1990): Modification of Neuronal Second Messenger Physiology: Expression of the Calcium Calmodulin Protein Kinase II Gene and the Yeast Adenylate Cyclase Gene in Neurons from HSV-1 Vectors. New York Academy of Sciences Conference on Central and Peripheral Significance of Neuropeptide Y and its Related Peptides.

Publications, continued:

Abstracts, continued:

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Freese, A., Finklestein, S., DiFiglia, M. (1990): Basic Fibroblast Growth Factor Attenuates NMDA Receptor Mediated Neurotoxicity in Striatal Neurons. Proceedings 20 th Annual Meeting, Society for Neuroscience, 16.88.10.

Swartz, K.J., During, M.J., Freese, A., Beal, M.F. (1990): Cerebral Synthesis and Release of Kynurenic Acid. Proceedings 20 th Annual Meeting Society for Neuroscience, 16:88:10.

Geller, A.I., Freese, A., O'Malley, K., During, M.J., Neve, R. (1990): Stable Modification of Rat Sympathetic Neuron Physiology and Neurotransmitter Release by Expression of Adenylate Cyclase from a HSV- 1 Vector. Proceedings 20 th Annual Meeting, Society for Neuroscience, 16:216:5.

During, M.J., Geller, A.I., Freese, A., Neve, R. (1990): Neuronal Expression of Parvalbumin and Calcium/Calmodulin Dependent Protein Kinase II from HSV-1 Vectors. Proceedings 20 th Annual Meeting, Society for Neuroscience , 16:216.4.

Freese, A., During, M.J., O'Malley, K., Geller, A.I. (1991): Expression of Tyrosine Hydroxylase in Striatal Cells with a HSV-1 Vector Causes Stable Production and Regulated Release of DOPA and Dopamine: Potential Gene Therapy for Parkinson's Disease. Proceedings 21 st Annual Meeting, Society for Neuroscience , 17:424.15.

Freese, A., During, M.J., O'Malley, K., Geller, A.I. (1992): Gene Therapy with HSV- I Vectors: Implications for Parkinson's Disease and Other Neurological Disorders. Annual Meeting of the American Association of Neurological Surgeons, 60:1179 (Selected for Discussion).

Freese, A., During, M.J., Geller, A.I. (1993): Modulation of Neuronal Adenylate Cyclase using HSV-1 Vectors: Implications for Neurological Disease. Annual Meeting of the American Association of Neurological Surgeons, 61:1165.

Freese, A., Swartz, K.J., During, M.J. (1994): Pharmacological Modulation of Kynurenic Acid, an Endogenous NMDA Receptor Antagonist: Neuroprotective Effects. Annual Meeting of the American Association of Neurological Surgeons, 62:1296.

Freese, A., During, M.J., O'Rourke, D.M., Geller, A.I. (1994): Gene Therapy with Modified Herpes Vectors: Implications for Molecular Neurosurgery. Annual Meeting of the American Association of Neurological Surgeons, 62:807.

Freese, A., Hurst, R.W., Zager, E.L., Flamm, E.S. (1994): Angiographic Vasospasm Associated with Hemorrhage from Arteriovenous Malformations. Annual Meeting of the American Association of Neurological Surgeons, 62:1038.

Freese, A., O'Connor, M.J., Kaplitt, M.J., O'Connor, W.M., During, M.J. (1994): Adeno-associated Virus Vector Mediated Gene Transfer into Human Hippocampal Slices. Annual Meeting of the American Epilepsy Society, 3.14.

Freese, A., Kaplitt, M.G., O'Connor, M.J., O'Connor, W.M., During, M.J. (1994): Gene Transfer into Human Hippocampal Slices with an Adeno-associated Virus Vector. Proceedings 24 th Annual Meeting, Society for Neuroscience , 592.15.

Kaplitt, M.G., Leone, P., Freese, A., Xiao, X., Pfaff, D.W., O'Malley, K.L., During, M.J. (1994): Adeno-associated Virus (AAV) Vectors Yield Safe Delivery and Long-term Expression of Potentially Therapeutic Genes in the Adult Mammalian Brain. Proceedings 24 th Annual Meeting, Society for Neuroscience , 602.11.

Publications, continued:

Abstracts, continued:

10

During, M.J., Kaplitt, M.G., Freese, A., Leone, P., Yiao, X., Samulski, R.J., Elsworth, J., Roth, R.H., Sladek, J., Jr., O'Malley, K.L., Redmond, D., Jr. (1995): In Vivo Gene Therapy of Parkinson's Disease in a Primate Model. Annual Meeting of the American Association of Neurological Surgeons, 63:701.

Randazzo, B.P., Freese, A., Kesari, S., Brown, S.M., MacLean, A.R., Fraser, N.W. (1995): Treatment of Cerebral Metastases with Herpes Simplex Virus One Mutant 1716: Culture and Animal Studies. Annual Meeting of the American Association of Neurological Surgeons, 63:1395.

Lippman, C., Welsh, F., Kaplitt, M.G., O'Connor, W.M., During, M.J., O'Connor, M.J., Freese, A. (1995): Adeno-associated Virus Mediated Human Heat Shock Protein 72 Gene Transfer into Neuronal Cultures. 12 th Annual Neuroscience Retreat, University of Pennsylvania.

Freese, A., O'Connor, M.J., During, M.J., Judy, K., Davidson, B. (1995): Adenovirus Vectors Result in Preferential Transgene Expression in Dividing Glial Cells. International Conference on Gene Therapy for CNS Disorders, 2.12.

Lippman, C., Welsh, F., Kaplitt, M.G., Abbey, M., O'Connor, W.M., During, M.J., O'Connor, M.J., Freese, A. (1995): Transfer of Human Heat Shock Protein-72 into Cultured CNS Cells using an Adeno-associated Virus Vector. International Conference on Gene Therapy for CNS Disorders, 4. 11.

Freese, A., Langer, D., Kaplitt, M.G., O'Connor, M.J., O'Connor, W.M., During, M.J. (1995): AAV Mediated Gene Transfer into Human Hippocampal Slices. International Conference on Gene Therapy for CNS Disorders. 4.33.

Redmond, D.E., Jr., O'Malley, K.L., Kaplitt, M.G., Samulski, R.J., Freese, A., Elsworth, J.D., Sladek, J.R., Jr., Leone, P., Xiao, X., Taylor, J.R., Roth, R.H., During, M.J. (1995): AAV Vector Gene Therapies in a Primate Parkinson's Model. International Conference on Gene Therapy for CNS Disorders, 3.10.

Langer, D.J., Barnathan, E.S., Freese, A., Welsh, F., Kariko, K. (1995): Neuronal Protection Mediated by Heat-Shock Protein-72 Gene Delivery: A Novel T7 Polymerase Based Gene Expression System. International Conference on Gene Therapy for CNS Disorders, 4.12.

Lippman, C., Welsh, F., Kaplitt, M.G., O'Connor, W.M., During, M.J., O'Connor, M.J., Freese, A. (1995): AAV-Vector Mediated Human Hsp-72 Gene Transfer into Cultured Cells. Proceedings 25 th Annual Meeting, Society for Neuroscience , 710.9.

Freese, A., During, M.J., Kaplitt, M.G., Davidson, B.L., O'Malley, K.L., Flamm, E.S., Gennarelli, T.A., Snyder, P. (1995): A Novel Gene Therapy Approach to Pituitary Adenomas. Proceedings 25 th Annual Meeting, Society for Neuroscience , 838.6.

Redmond, D.E., Jr., O'Malley, K.L., Kaplitt, M.J., Samulski, R.J., Elsworth, J.D., Sladek, J.R., Jr., Leone, P., Xiao, X., Freese, A., Taylor, J.R., Roth, R.H., During, M.J. (1995): AAV Vectored Gene Therapy in Primate Parkinson's Model. Proceedings 25 th Annual Meeting, Society for Neuroscience, 224.22.

Publications, continued:

Abstracts, continued:

11

During, M.J., Choi-Lundberg, D., Leone, P., Lin, Q., Kaplitt, M.G., Xiao, X., Samulski, R.J., Freese, A., Hoffer, P., Roth, R.H., Elsworth, J.D., Sladek, J.R., Jr., O'Malley, K.L., Federoff, H.J., Redmond, D.E., Jr., Bohn, M.C. (1995): Neuroprotection and Neuroregeneration in Rodent and Primate Parkinson's Models Using AAV Vectors Expressing GDNF. Proceedings 25 th Annual Meeting, Society for Neuroscience , 225.9.

Freese, A., Flamm, E.S., During, M.J., Kaplitt, M.G., Davidson, B.L., O'Malley, K., Gennarelli, T.A., Snyder, P.J. (1995): A Novel Gene Therapy Approach to Prolactinomas and other Pituitary Adenomas. Annual Meeting of the Congress of Neurological Surgeons, Abstract 231.

Freese, A., O'Connor, M.J., Langer, D., Kaplitt, M.G., O'Connor, W.M., During, M.J. (1995): Gene Transfer into Human Hippocampal tissue using an Adeno-associated Virus Vector: Prospects for Gene Therapy in Focal Epilepsy. Annual Meeting of the Congress of Neurological Surgeons, Abstract 748.

Lippman, C., Welsh, F., Kaplitt, M., O'Connor, W.M., During, M.J., O'Connor, M.J., Freese, A. (1996): Demonstration of a Direct Neuroprotective Function of Human Heat Shock Protein-72 in Cultured CNS Neurons using an Adeno-associated Virus Vector Expressing the Hsp-72 Gene. Annual Meeting of the American Association of Neurological Surgeons. Abstract 1109.

Freese, A., Leone P., Choi-Lundberg D., Federoff, H.J., Redmond, D.E., During, M.J. (1996): A Gene Therapy Approach to Parkinson's Disease Using an AAV Vector Expressing Glial Derived Neurotrophic Factor (GDNF). Annual Meeting of the American Association of Neurological Surgeons, Abstract 1320.

Freese, A., During, M.J., Lowen, G., O'Connor, W.M., O'Connor, M.J., Davidson, B.L. (1996): Adenovirus Vector-Mediated Delivery of the Tyrosine Hydroxylase Gene into Striatal Cells: Implications for Gene Therapy in Parkinson's Disease. Annual Meeting of the American Association of Neurological Surgeons, Abstract 742.

Schnee, CL, Freese, A., Weil, R.J., Marcotte, P.J. (1996): Morbidity and Fusion Outcome of Autologous Iliac Crest Bone Graft for Anterior Cervical Reconstruction. Annual Meeting of the Congress of Neurological Surgeons, Abstract 739.

Schnee, C.L. Weil, R.J., Freese, A., Marcotte, P.J. (1996): Evaluation of Operative Technique for Thoracolumbar Spinal Neoplasms. Annual Meeting of the Congress of Neurological Surgeons, Abstract 275.

Freese, A. (1997): A Historical Perspective on Gene Therapy: Implications for Molecular Neurosurgery. Annual Meeting of the American Association of Neurological Surgeons, Abstract 839.

Abbey, M., Davidson, B.L., Cox, R., Hurst, R., Langer, D., Riina, H., O'Connor, M.J., Freese, A. (1997): Nitric Oxide Synthase Gene Transfer into Human Cerebral Vascular Smooth Muscle Cells: Prospects for Genetic Intervention in Vasospasm. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1036.

Freese, A., Figuereo, S., Wilensky, R., During, M.J., Riina, H., O'Connor, M.J., Hurst, R.J. (1997): Selective Endovascular Delivery of Gene Transfer Systems into the Brain: Prospects for Targeting of Gene Therapy in Neurological Disorders. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1219.

Publications, continued:

Abstracts, continued:

12

Weil, R.J., Schnee, C., Freese, A., Marcotte, P.J. (1997): Anterior Cervical Decompression and Fusion for Cervical Spondylotic Myelopathy, Annual Meeting of the American Association of Neurological Surgeons, Abstract 1350.

O'Connor, W.M., Davidson, B.L., Kaplitt, M.G., Abbey, M.V., During, M.J., Leone, P., Langer, D., O'Connor, M.J., Freese, A. (1997): Adenovirus Vector Mediated Gene Transfer into Human Epileptogenic Brain Slices. 22 nd International Epilepsy Congress Proceedings, (in Epilepsia: 38:203).

Freese, A., Young, D.D., Liu, C.Y., Leone, P., Davidson, B.L., Silver, D., Xie, H., During, M.J. (1997): Phenotypic Recovery in Parkinsonian Rats: Relationship Between numbers of Transduced Cells and Behavior Using an Adenoviral Vector Expressing Tyrosine Hydroxylase. Proceedings 27 th Annual Meeting, Society for Neuroscience , Abstract 211.3

During, M.J., Nass, D.J., Xie, H., Freese, A., Leone, P. (1997): Towards Gene Therapy of Epilepsy: Comparison of GAD-65, GABA-A Delta Subunit, and GDNF Vectors in a Rat kainate model. Proceedings 27 th Annual Meeting, Society for Neuroscience, Abstract 319.8.

O'Connor, M.J., Weil, R.J., Liporace, J., Freese, A., Sperling, M.R. (1998): Multiple Subpial Transactions in Eloquent Cortex. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1289.

O'Connor, M.J., Sperling, M.R., Liporace, J., Sirven J., Barry, E., Freese, A. (1998): Results of Long Term Follow up of 405 Temporal Lobectomies over a Twenty Year Period. Annual Meeting of the American Association of Neurological Surgeons, Abstract 714.

Freese, A., O'Connor, M.J., Leone, P., Ness, D.J., Xie, H., During, M.J. (1998): Genetic Intervention in an Animal Model of Epilepsy: Effects of Transfer of Genes Encoding Glutamic Acid Decarboxylase, a GABA Receptor Subunit, or Glial Cell-derived Neurotrophic Factor. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1263.

Freese, A., Young, D.D., Silver, D., Liu, C.Y., Davidson, B.L., O'Connor, M.J., Leone, P., During, M.J. (1998): Correlation Between Number of Transduced Cells and Behavioral Recovery in a Rat Parkinson's Disease Model Following In Vivo Gene Therapy. Annual Meeting of the American Association of Neurological Surgeons, Abstract 825.

During, M.J., Freese, A., Sorgi, F.L., Huang, L., Bilaniuk, L., Wang, Z., Mayes, L.C., Seashore, M.R., Mee, E., Leone, P. (1998): Intraventricular Delivery for Gene Therapy in the Fatal, Pediatric Neurogenetic Disorder, Canavan Disease. Annual Meeting of the American Association of Neurological Surgeons, Abstract 821.

During, M.J., Freese, A., Woodgate, A.M., Lipski, J., Young, D., Xu, R. (1998): Transfer of the c-Jun Gene into PC12 Cells Induces Differentiation into a Neuronal-like Phenotype. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1351.

During, M.J., Freese, A., Woodgate, A.M., Lipski, J., Young, D., Xu, R. (1998): Transfer of the c-Jun Gene into PC12 Cells Induces Differentiation into a Neuronal-like Phenotype. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1351.

Publications, continued:

Abstracts, continued:

13

During, M.J., Dragunow, M., Woodgate, A.M., Xu, R., Freese, A. (1998): The Phosphorylated State of c-Jun Following Okadaic Acid Induced Apoptosis and Nerve Growth Factor-Induced Sprouting in PC12 Cells. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1143.

Simeone, F.A., Freese, A. (1998): The opportunity costs of training to become a neuro-surgeon: relevance for the expectation of appropriate compensation. Annual Meeting of the American Association of Neurological Surgeons, Abstract 726.

Freese, A. (1998): Prospects of Gene therapy Approaches to Neuromodulation. 4 th International Congress of the International Neuromodulation Society.

Leone, P., Duncan, C., Barolat, G., Freese, A., Seashore, M., Sorge, F., Cherniske, E., Janson, C.G., During, M.J. (1998): Gene Therapy of Canavan Disease uisng LPD/pAAV-ASPA: A Phase 1 Study. Proceedings 28 th Annual Meeting, Society for Neuroscience, Abstract 405.4.

Simeone, F.A., Freese, A. (1999): The Devaluation of Neurosurgical Procedures by Managed Care and the Relevance of the Consumer Price Index over the Past Decade. Annual Meeting of the American Association of Neurological Surgeons, Abstract 752.

Abbey, M.V., Freese, A., Bagasra, O., O’Connor, W.M., Memoli, M., Van Bockstaele, E., O’Connor, M.J. (1999): In Situ rtPCR: A Novel Approach towards Evaluating Gene Expression in Human Brain Tissue. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1352.

McPhee, S.J., Fenu.S., Xu, R., Mastakov, M., Fan, X, Freese, A., During, M.J., Leone, P. (1999): In Vivo Analysis of Tyrosine Hydroxylase Expression Cassettes in the 6-OHDA Parkinsonian Rat Model Using AAV Vectors: A Repeated Injection Paradigm. Proceedings 2 nd Annual Meeting of the American Society of Gene Therapy Abstract 200.

Harrop, J., Poulsen, D.J., Maragakis, N.J., Xiao, W., Liu, Y., Luo, J., Rothstein, J.D., Freese, A., During, M.J. (2000): Transduction of Neurons and Astrocytes within the Rat Spinal Cord using Recombinant AAV-2 and Pseudotyped AAV-5. Proceedings 30 th

Annual Meeting, Society for Neuroscience, Abstract 259.7Harrop, J.S., Poulsen, D., Maragakis, N., Xiao, W., Liu, Y., Liu, J., Rothstein, J., Freese,

A., During, M. (2000): Use of a Gene Therapy Vector (recombinant AAV) to Transduce Neurons and Astrocytes within the Rat Spinal Cord Parenchyma. Annual Meeting of the Congress of Neurological Surgeons, Abstract 279.

Leone, P., Freese, A., Latsko, M., McPhee, S., During, M.J., Janson, C.G. (2001): Comparison of Viral and Non-Viral Vectors for Gene Therapy of Canavan Disease. Proceedings of the European Metabolic Group Meeting, Amsterdam.

Liouterman, L., During, M.J., McPhee, S.W.J., Freese, A., Janson, C.G., Horst, R., Peschle, C., Valtieri, M., Leone, P. (2001): Transplantation of Human Hematopoeitic Stem Cells into Rat Brain: Analysis of Cell Survival and Differentiation. Proceedings 31 st Annual Meeting, Society for Neuroscience, Abstract 405.4.

Publications, continued:

Abstracts, continued:

14

Leone, P., Latsko, M., Haselgrove, J., McPhee, S.W.J., Janson, C.G., Jiao, X.Y., Liouterman, L., Francis, J., Young, D., Lawlor, P.A., Fitzsimons, H., Raniga, S., Bilaniuk, L, Wang, Z., Grant, M., Liu, Y., During, M.J., Freese, A. (2001): Gene Therapy of Canavan Disease using AAV Vectors: A Phase 1 Clinical Trial. Proceedings 31 st Annual Meeting, Society for Neuroscience .

Freese, A., Latsko, M., McPhee, S., Janson, C., Bilaniak, L., During, M., Leone, P., (2002): Adenoassociated Virus Vector Gene Transfer into the Human Brain: A Phase1 Trial for Patients with Canavan Disease. Annual Meeting of the American Association of Neurological Surgeons, Abstract 710.

Leone, P., McPhee, S.W.J., Janson, C.G., Liouterman, L., Freese, A. (2002): Brain Gene Transfer using AAV Vectors in the Canavan (Tremor) Rat Model and in Children Affected by Canavan Disease: Targeted Development of Preclinical and Clinical Studies. XIVth International Workshop on Genetic Systems in the Rat (Kyoto, Japan).

Freese, A., Liouterman, Liouterman, L., During, M., McPhee, S., Janson, C., Leone, P. (2002): Transplantation of Human Hematopoeitic Stem Cells into Rat Brain; Analysis of Cell Survival and Differentiation. Annual Meeting of the American Association of Neurological Surgeons, Abstract 1132.

Harrop, J., Poulson, D., Darling, M., Freese, A., Maragakis, N., Rothstein, J. (2002): Recombinant AAV Transduces Neurons and Astrocytes within the Rat Spinal Cord. Annual Meeting of the American Associations of Neurological Surgeons, Abstract 768.

Leone, P., Janson, C.G., Freese, A., Samulski, J., Haselgrove, J. Wang, D.J., Bilaniuk, L. (2002): Terapia Genica Nei Pazienti con Malattia Metabolica: Il Modello della Malattia di Canavan. Milanopediatria 2002 (Milan, Italy).

Book Chapters, Books and Special Journals:Freese, A., Thilly, W.G. (eds). (1988): Biotechnology Processing: Human Serum Albumin

Production, Applied Biology Reviews Series, vol. 1, Massachusetts Institute of Technology, Cambridge, MA.also co-authored the following chapters in the above book:Chapter 2: ‘Human Serum Albumin: Properties and Applications’: Freese, A.,

McCafferty, F., Schaecter, J.,Van Amsterdam, J., de Moreas, C.A., Connors, N.C., Wu, D.Y., Kim, S.K., Chang, M., Weist, J.;

Chapter 6: ‘Mammalian Cell Technology’: Wu, D.Y., Kim, S.K., Chang, M., Weist, J., Freese, A.;

Chapter 7: ‘The Development of a Transgenic Chicken’: Donahue, B., Reynolds, C., Freese, A.

Sabel, B.S., Freese, A., During, M.J. (1990): Controlled-Release Dopamine Polymers as a Novel Approach to the Treatment of Parkinson's Disease. Parkinson's Disease, Advances in Neurology, (Streifler, M.B. et. al., eds), Raven Press, pp. 521-526.

During, M.J., Heyes, M.P., Freese, A., Swartz, K.J., Matson, W.R., Markey, S.P., Martin, J.B., Roth, R.H. (1991): Indolic and Kynurenine Pathway Metabolites of Tryptophan in Rat Brain: Effects of Precursor Availability on In Vivo Release. Tryptophan Research (Schwarcz, R., Young, S.N., Brown, R.R., eds.), Plenum Press, pp. 535-539.

Publications, continued:

Book Chapters, Books and Special Journals:

15

Vecsei, L, Freese, A., Swartz, K.J., Beal, M.F. (eds., 1992): Neurological Disorders: Novel Experimental and Therapeutic Strategies. Ellis Horwood, Simon and Schuster International Group, Hemel Hempstead, Herts, England.

Freese, A., Flamm, E.S., Cooperman, B.S., Wilson, J.M. (eds., 1995): Proceedings of the International Conference on Gene Therapy for CNS Disorders. CME Office, University of Pennsylvania, Philadelphia, PA.

Freese, A. (guest editor, 1997): Gene Therapy for Parkinson's Disease: Rationale, Prospects and Limitations. Experimental Neurology, special issue, vol. 144, number 1.

Freese, A. (1999): Restorative Gene Therapy Approaches to Parkinson’s Disease. Parkinson’s Disease and Parkinsonian Syndromes. (Stern, M.B., Hurtig, H.I. eds.). W.B. Saunders Co., Philadelphia, PA, pp. 537-548.

Freese, A., Leone, P., Barolat, G., During, M.J. (1999): Genetic Intervention in Children with Canavan Disease: A Model for Gene Therapy of Neurometabolic Disorders. Neuronal Precursor Cell Biology and Application for Treatment of Inborn Error of Metabolism. (Sakuragawa, N. ed). National Center of Neurology and Psychiatry, Tokyo, Japan pp. 216-221.

Freese, A. (1999): Gene Therapy Approaches to Parkinson's Disease. Movement Disorder Surgery (Lozano, A.M., ed). Karger, Basel, vol 15 pp. 381-394.

Marcotte, P., Freese, A. (2000): Spinal Injury, in The Intensive Care Unit Manual (Lanken, P.N., ed.), W.B. Saunders Co., Philadelphia, pp.1077-1084.

Freese, A., Simeone, F.A., Leone, P., and Janson, C. (2005): Principles of Molecular Neurosurgery. (guest editor of volume to be published in Lunsford, L.D. ed, Progress in Neurological Surgery, series) Karger Medical & Scientific Publishers: New York, in press, (a 660 page volume).

Theses:

B.A. Honors Thesis, Harvard University, Department of Biochemical Sciences: The Effects of Coprostanol and Other Related Sterols on the Growth and Membranes of Mycoplasma capricolum, Thesis Advisor: Professor Konrad Bloch, Ph.D., Harvard University (1981).

M.D. Honors Thesis, Harvard Medical School, Division of Health Sciences and Technology: Drug and Gene Delivery into the Central Nervous System, Thesis Advisor: Robert Langer,Sc.D., Massachusetts Institute of Technology (1990).

Ph.D. Thesis, Massachusetts Institute of Technology, Division of Health Sciences and Technology: Excitotoxic Mechanisms in Huntington's Disease, Thesis Advisors: Joseph B. Martin, M.D., Ph.D. and Marian DiFiglia, Ph.D., Harvard Medical School and Massachusetts Institute of Technology (1992).

Publications, continued:

16

Patents and Invention Disclosures:

Sabel, B.A., Freese, A., Saltzman, W.M., Langer, R. (1989): Controlled Drug DeliverySystem for the Treatment of Neural Disorders. Patent Number 4,883,666; Date of Patent: Nov. 28, 1989, U.S. Department of Commerce.

Sabel, B.A., Freese, A., Langer, R. (1992): Extended Drug Delivery of Small, Water Soluble Molecules. Patent Number 5,114,719; Date of Patent: May 19, 1992, U.S. Department of Commerce.

Sabel, B.A., Freese, A., Saltzman W.M., Langer R.S. (1993): Controlled Drug Delivery System for Treatment of Neural Disorders. European Patent Number 88106935.5, Patent Issued.

Sabel, B.A., Freese, A. (1993): Extended Drug Delivery of Small, Water-Soluble Molecules. European Patent Number 90116768.4, Patent issued.

Sabel, B.A., Freese, A., Saltzman, W.M., During, M.J. (1997): Polymeric Device for Controlled Drug Delivery to the CNS; Patent Number 5,601,835; Date of Patent: Feb. 11, 1997, U.S. Department of Commerce.

Beal, M.F., Freese, A., During, M.J., Swartz, K.J. : (2001): Treatment of Neurological Disease by Increasing Brain Concentrations of Kynurenic Acid, Patent Number 6,265,442; Date of Patent: July 24, 2001, U.S. Department of Commerce.

Freese, A., Anderson, D.G. (2003): A Novel Anterior Cervical Plating System, patent application submitted.

Seminars and Presentations:

September, 1986: ‘Phosphatidylcholine Turnover in a Neural Tumor Cell Line’, Annual Harvard Medical School M.D., Ph.D. Program Retreat, Marine Biological Laboratories, Woods Hole, MA.

April, 1987: ‘Safety Issues Relating to Aspartame Consumption’, presented at the Case Report on Phenylalanine Production (for the Synthesis of Aspartame), to Industry and University Representatives, Dept. Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge, MA.

May, 1987: ‘Therapeutic Alternatives to Tissue Plasminogen Activator’, Summary Perspective on Tissue Plasminogen Activator, presented at the Case Report on Tissue Plasminogen Activator, to Industry and University Representatives, Dept. Applied Biological Sciences, Massachusetts Institute of Technology, Cambridge, MA.

August, 1987: ‘Industrial Scale Production of Human Serum Albumin through the Development of a Transgenic Chicken’, presented with Prof. W.G. Thilly to Campbell Soup Co., sponsored by the MIT Industrial Liaison Program, Cambridge, MA.

November, 1987: ‘Towards a Tissue Culture Model for Huntington's Disease’, Neurology Research Seminar Series, Dept. Neurology, Mass. General Hospital, Boston, MA.

March, 1988: ‘Intrastriatal Quinolinic Acid Levels following Tryptophan Administration:Pathogenetic Link to Huntington's Disease?’, Neurology Research Seminar Series, Massachusetts General Hospital, Boston, MA.

Seminars and Presentations, continued:

17

June, 1988: ‘Drug Delivery Systems for Neurological Disorders’, University/Incubator Spin Off Companies Conference, Westin Hotel, Boston, MA, hosted by the MIT Office of Technology Licensing.

October, 1988: ‘Characterization and Mechanism of Glutamate Neurotoxicity in Primary Striatal Cultures’, Whitehead Institute, Massachusetts Institute of Technology, Cambridge, MA.

October, 1989: ‘Excitotoxic Mechanisms in Huntington's Disease and the Kynurenine Pathway’, Massachusetts Institutes of Technology, Division of Health Sciences and Technology, Cambridge, MA.

April, 1991: ‘Brain Tissue Transplantation’, Department of Surgery, University of Pennsylvania, Philadelphia, PA.

November, 1991: ‘Excitotoxic Mechanisms in Huntington's Disease' Ph.D. Thesis Defense, Massachusetts Institute of Technology, Cambridge, MA.

November, 1992: 'Novel Therapeutic Approaches to Parkinson's Disease: Drug and Gene Delivery Systems’, Grand Rounds, Departments of Neurology and Neurosurgery, University of Pennsylvania, Philadelphia, PA.

November, 1992: ‘Spinal Epidural Abscesses’, Department of Medicine, University of Pennsylvania, Philadelphia, PA.

March, 1993: ‘Neurosurgical Approaches to Parkinson’s Disease: Past, Present and Future’, Surgical Grand Rounds, Graduate Hospital, Philadelphia, PA.

November, 1993: ‘Pharmacology of the Kynurenenine Pathway: EndogenousNeuroprotection’, Wyeth Ayerst Laboratories, Radnor, PA.

March, 1993: ‘Neurosurgical Approaches to Parkinson’s Disease: Past, Present and Future’, Surgical Grand Rounds, Graduate Hospital, Philadelphia, PA.

February, 1994: ‘Gene Transfer into the CNS with Modified Herpes Vectors’, Wistar Institute, Philadelphia, PA.

April, 1994: ‘Viral Vector Based Gene Delivery into the Brain’, Section on Functional and Stereotactic Surgery, American Association for Neurological Surgeons, San Diego, CA.

April, 1994: ‘Molecular Biology Approaches to Studying Neurological Disorders’ Bockus Research Laboratories, Philadelphia, PA.

December, 1994: ‘Gene Therapy Approaches to CNS Disorders’, START Technology Partnership, Philadelphia, PA.

April, 1994: ‘Prospects for In Vivo Gene Therapy for Parkinson's Disease’, Sandoz, Inc., (presentation at Graduate Hospital, Philadelphia, PA)

June, 1995: ‘Gene Therapy Approaches to Pituitary Adenomas’; presentation at the International Conference on Gene Therapy for CNS Disorders, Philadelphia, PA.

October, 1995: ‘Gene Transfer into Human Hippocampal Tissue using an Adeno-associated Virus Vector: Prospects for Gene Therapy in Focal Epilepsy’; presentation at The Annual Meeting of the Congress of Neurosurgical Surgeons, San Francisco, CA.

January, 1996: ‘Modulation of Dopamine Systems in the Central Nervous System: Gene Therapy Approaches,’ Institute for Human Gene Therapy, University of Pennsylvania, Genetics Affinity Group, Philadelphia, PA.

January, 1996: ‘Gene Therapy Approaches to Pituitary Adenomas’, the Brain Tumor Group, Wistar Institute, Philadelphia, PA.

Seminars and Presentations, continued:March, 1996: ‘Clinical Implications of Genetic Modulation of CNS Dopamine Systems’,

First Annual Ernst Freese Memorial Lecture; National Center for Human Genome 18

Research and National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

April, 1996: ‘Overview of Gene Therapy for Parkinson's Disease’, The 1st Meeting of the Parkinson's Disease Gene Therapy Consortium, Washington, D.C.

April, 1996: ‘Clinical Implications of Genetic Modulation of CNS Dopamine Systems’, Neurosurgery Grand Rounds, University of Iowa School of Medicine, Iowa City, IA.

April, 1996: Discussant on ‘Gene Therapy for Brain Tumors by Controlled Expression of Interleukin-lß-Converting Enzyme’, Annual Meeting of the American Association of Neurological Surgeons, Minneapolis, MN.

April, 1996: ‘Adenovirus Vector-Mediated Delivery of the Tyrosine Hydroxylase Gene into Striatal Cells: Implications for Gene Therapy in Parkinson's Disease’, presentation at the Annual Meeting of the American Association of Neurological Surgeons, Minneapolis, MN.

December, 1996: ‘Prospects for Restorative Molecular Neurosurgery’, Grand Rounds, Department of Neurosurgery, Washington University, St. Louis, MO.

February, 1997: ‘Restorative Molecular Neurosurgery: Prospects and Limitations’, Grand Rounds, Department of Neurosurgery, University of California, San Francisco, CA;

April, 1997: ‘A Historical Perspective on Gene Therapy: Implications for Molecular Neurosurgery’, Annual Meeting of the American Association of Neurological Surgeons, Denver, CO.

July, 1997: ‘Gene Therapy for Neurological Disorders’, Davis Biotechnology Associates, Los Angeles, CA.

September, 1997: ‘The Present and Future of Gene Therapy for Neurological Disorders’,platform presentation at the Pennsylvania Neurosurgical Society, Hershey, PA.

April, 1998: ‘Phenotypic Recovery in Parkinsonian Rats: Relationship Between Number of Transduced Cells and Behavior Using an Adenoviral Vector Expressing Tyrosine Hydroxylase’, Annual Meeting of the American Association of Neurological Surgeons, Philadelphia, PA.

April, 1998: ‘Intraventricular Delivery for Gene Therapy in the Fatal, Pediatric Neurogenetic Disorder, Canavan Disease’, Annual Meeting of the American Association of Neurological Surgeons, Philadelphia, PA.

September, 1998: ‘Prospects of Gene Therapy Approaches to Neuromodulation’, 4th International Congress of the International Neuromodulation Society, Lucerne, Switzerland.

September, 1998: ‘Gene Therapy of CNS Diseases,’ Progen, Inc., Heidelberg, Germany.November, 1998: ‘What’s Ahead: Potential for Gene Therapy of Pituitary Adenomas’, The

Atlantic Seaboard Pituitary Conference, Philadelphia, PA.December, 1998: ‘The Future of Gene Therapy’, The 10th Pan-Philadelphia Neurosurgical

Conference, Philadelphia, PA.December, 1998: ‘Gene Therapy for Neurosurgical Disorders’, Surgical Grand Rounds,

Thomas Jefferson University, Philadelphia, PA.December, 1998: ‘Prospects for Endovascular Delivery of Gene Therapy to the Brain’,

Cordis Endovascular, Miami Lakes, FL.

Seminars and Presentations, continued:January, 1999: ‘Gene Therapy for Neurological Disorders: Science Fact, not Fiction’,

Neurosurgery Grand Rounds, Temple University, Philadelphia, PA.

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January, 1999: ‘Gene Therapy for Neurosurgery’, Grand Rounds, Department of Surgery, Graduate Hospital/Hahnemann University, Philadelphia, PA.

January, 1999: ‘Stereotactic Approaches to Gene Therapy of CNS Disorders’, Radionics, Inc., Burlington, MA.

February, 1999: ‘Genetic Intervention in Children with Canavan Disease: A Model for Gene Therapy of Neurometabolic Disorders’, International Workshop on Neuronal Precursor Cell Biology and Application for Treatment of Inborn Error of Metabolism, Tokyo, Japan.

February, 1999: ‘Gene Therapy of CNS Disorders’, Neurosurgery Grand Rounds, Sinjeako University, Tokyo, Japan.

March, 1999: ‘Gene Therapy Approaches to Neurological Disease’, Presentation toGenzyme, Inc., Cambridge, MA.

May, 1999: ‘Gene Therapy for Neurological Disorders’, Neurology Grand Rounds, Thomas Jefferson University, Philadelphia, PA.

July, 1999: 'Gene Therapy for Neurosurgical Diseases', Neurology/Neurosurgery Grand Rounds, Medical College of Wisconsin, Milwaukee, WI.

November, 1999: 'Prospects for Genetic Intervention in Neurological Diseases' Neurosurgery Grand Rounds, Medical University of South Carolina, Charleston, SC

December, 1999: 'Gene Therapy in Canavan Disease' The 11th Pan Philadelphia Neurosurgical Conference, Philadelphia, PA.

February, 2000: 'Gene Therapy for Neurosurgical Diseases - Science Fiction or Science Fact' Neurosurgery Grand Rounds, Medical University of South Carolina, Charleston, SC

December, 2000: 'Molecular Neurosurgery: Science Fiction or Science Fact?', Neurosurgery Grand Rounds and Visiting Professor, SUNY, Syracuse

February, 2001: 'Gene Therapy for Neurosurgical Diseases', Neurosurgery Grand Rounds, Thomas Jefferson University, Philadelphia, PA

March, 2001: 'Gene Therapy for Neurosurgical Diseases: Science Fact vs. Science Fiction', Neurosurgery Grand Rounds, Henry Ford Hospital, Detroit, MI

April 2002: 'Gene Therapy for Canavan Disease with an AAV Vector. American Association of Neurologic Surgeons, Chicago, IL

May 2002: 'Gene Therapy for Spinal Disorders Sofamor Danek Think Tank, Amelia Island, FL

November, 2002: ‘A Neurosurgeon Wandering Through the Fields of Gene Therapy: Lessons Learned’, University of North Carolina, Chapel Hill, Gene Therapy Center and Department of Neurosurgery, Grand Rounds

February, 2003: 'Disk Replacement Surgery, Indications vs. Hype' Grand Rounds, Thomas Jefferson University, Philadelphia, PA

August, 2003: ‘Gene Therapy of Neurological Disorders’, University of Heidelberg, Heidelberg, Germany, scheduled presentation.

September, 2003: ‘Gene Therapy and Cervical Spinal Disorders’, Harvard Medical School , Cervical Think Tank, Boston MA

Seminars and Presentations, continued:December, 2003: ‘A Neurosurgeon’s Travels in Gene Therapy: It Doesn’t Take a Gene

Therapist to do Brain Surgery.’Grand Rounds, University of Minnesota (Minneapolis), Department of Neurosurgery, Minneapolis, MN

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February, 2004: ‘Disk Replacement Surgery: An Overview’, Grand Rounds, University of Pennsylvania Department of Orthopaedic Surgery, Philadelphia, PA.

October, 2004: ‘Gene Therapy and Canavan Disease’, Keynote Speaker at annual Canavan Foundation Gala, Chicago, IL

December, 2004: ‘Gene Therapy for Neurosurgical and Spinal Disorders’, University of Chicago, Chicago, IL (scheduled).

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