NEURONAL CELL THERAPY FOR PARKINSONS DISEASE

The unique properties of hNT-Neurons, pure human post mitotic neuronal cells, justify their development as a local delivery system for dopaminergic factors of therapeutic benefit in Parkinson's disease. Previous research demonstrates that hNT-Neurons are transplantable and transfectable. Transplants of hNT-neurons into rodent brain show cell survival, neuronal phenotype, and functional integration. Transfection studies suggest that recombinant hNT-neurons can achieve efficient and stable gene expression. The aims of this proposal are to: evaluate the endogenous dopaminergic properties of hNT-Neurons; enhance dopaminergic activity with enzymes, cofactors or growth factors; survey additional clones and subclones for highest production; and identify the optimal gene construct to transfect for therapeutic purposes. Enzyme expression and L-dopa production will be measured using immunochemical and biochemical assays. This research strategy allows for characterization and optimization of the dopaminergic properties of hNT-Neurons in vitro prior to animal studies planned in Phase II. Functional, dopaminergic, human neuronal cells are scientifically promising, technologically superior to other cell systems, and commercially viable as a treatment for Parkinson's disease. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 502 --PROJECT NUMBER......1 R43 NS36505-01 INVESTIGATOR NAME/ADDRESS FY 97 OZGUZ, VOLKAN IRG/INTRAMURAL UNIT..ZRG1 IRVINE SENSORS CORPORATION AWARD AMOUNT......... $99,572 3001 REDHILL AVE, BLDG #3 COSTA MESA, CA 92626 PERFORMING ORGANIZATION: IRVINE SENSORS CORPORATION TITLE A FLEXIBLE, ULTRATHIN CIRCUIT TO ANALYZE SLEEP DISORDERS ABSTRACT: Irvine Sensors Corporation proposes an ultrathin, flexible, lightweight and unobtrusive Band-Aid-like electronic suitable for the analysis of fatigue, sleep disorders and other biomedical sensing applications. The proposed circuit would be affixed to the human eyebrow or temple to collect data from a small piezoelectric or coil-based sensor placed on the eyelid. Ultrafine wiring will connect the sensor to the data collection unit. A paperlike thin-film battery will provide power to the memory, A/D converter and sensor suite. A low-power RF unit will be used to communicate with a receiver worn on a belt. Research has demonstrated a correlation between eyelid activity and fatigue, loss of alertness and loss of vigilance. The proposed accurate, cost-effective, reliable ambulatory monitoring device would facilitate patient compliance in in-home and remote studies, contribute to the identification and treatment of undiagnosed sleep disorders and sleep loss and reduce the danger and cost of catastrophic accidents. The successful completion of the proposed effort will enable a revolutionary approach to electronic packaging. The proposed invention will have significant commercial application is the following broad categories of technology application: (1) conformal packaging; (2) space saving, (3) heat transfer enhancement; (4) capacitance reduction; and (5) environmental reliability. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 503 --PROJECT NUMBER......1 R43 NS36507-01 INVESTIGATOR NAME/ADDRESS FY 97 ZHOU, LI-MING IRG/INTRAMURAL UNIT..ZRG1 COGNETIX INC AWARD AMOUNT......... $95,368 807 E SOUTH TEMPLE, SUITE 310 SALT LAKE CITY, UT 84102 PERFORMING ORGANIZATION: COGNETIX, INC. TITLE CONANTOKINS FOR TREATMENT OF EPILEPSY ABSTRACT: DESCRIPTION (Investigator's Abstract): (They) propose to characterize conantokin peptides for treatment of epilepsy. Conantokins, a family of small peptides (17-27 amino acids) isolated from the venom of fish-hunting cone snails, are specific antagonists of NMDA receptors in the mammalian central nervous system. Conantokins inhibit NMDA-elicited currents and NMDA- stimulated cyclic GMP formation. Their laboratories performed the first in vivo studies showing that conantokins exhibit a potent antiseizure activity in animals. Conantokins were shown to be some of the most potent compounds ever tested in the Frings audiogenic seizure-susceptible mouse model. In addition, conantokins showed low neurotoxicity, as determined by relating the toxic dose (rotorod performance) to the effective dose. Therefore, conantokins represent a unique, highly potent and novel class of compounds for treatment of CNS disorders. In Phase I, we propose to: test conantokins for antiseizure activity using three different experimental animal models; compare the in vivo antiseizure activity of conantokins with their in vitro receptor binding activity; identify and evaluate new natural conantokins; and synthesize chimeras of conantokins to initiate structure function studies. In Phase II, more extensive in vivo characterization of conantokins for treatment of seizure disorders will be carried out. Moreover, they will establish a program for synthesis of conantokin peptidomimetics, which should increase the bioavailability of these molecules. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 504 --PROJECT NUMBER......1 R43 NS36520-01 INVESTIGATOR NAME/ADDRESS FY 97 ALSTEN, CHRISTOPHER R IRG/INTRAMURAL UNIT..ZRG1 INNER HEALTH, INC AWARD AMOUNT......... $100,000 PO BOX 1609 IDYLLWILD, CA 92549-1609 PERFORMING ORGANIZATION: INNER HEALTH, INC. TITLE MULTIFACTOR 3D SOUND ENHANCED INSOMNIA TREATMENT PROGRAM ABSTRACT: (Investigator's Abstract): The purpose of this study is to determine the feasibiligy and gather preliminary data on the efficacy of an inexpersive, easily deliverable, home use, nonpharmacological treatment program for general insomnia using subjective and objective measures (polysomnography and actigraphy) and a repeated measures design. The treatment program is based around an audiocassette integrating relaxation techniques, cognitive restructuring, imagery and other psychological techniques along with traditional sleep hygiene and other behavioral treatment materals organized in a "self-directed" system. This prototype audiocassette Program incorporates a new 3-Dimensional "virtual reality" like sound technology that enhances imagery, realism and, it is believed, efficacy. Elements of the prototype program has successfully been piloted in clinical settings with psychiatric patients, and has been used to train Air Force aircrew members to sleep more effectively in spite of circadian desynchronization. This study would be the first step leading to FDA approvable claims for the program's ability to alleviate insomnia. This would provide an effective and easy to use alternative to sedative-hypnotics which will have significant market potential. $ = TOTAL AWARD AMTS & NOT LIMITED TO PORTION OF PROJECT RELATED TO SUBJECT OF SEARCH SUBPROJECT $ = TOTAL AWARD AMOUNT DIVIDED BY NUMBER OF SUBPROJECTS SOURCE: CRISP FORMAT F FY 97 LAST UPDATE 04-07-98 1QUERY 1536 ID SEARCH 06/01/98 PAGE 505 --PROJECT NUMBER......1 R43 NS36878-01 INVESTIGATOR NAME/ADDRESS FY 97 MARGOLIN, LEE D IRG/INTRAMURAL UNIT..ZDA1 FHC INC AWARD AMOUNT......... $100,000 9 MAIN STREET BOWDOINHAM, ME 04008 PERFORMING ORGANIZATION: FHC, INC. TITLE TRIMODAL ELECTRODE SYSTEM FOR PALLIDOTOMY AND THALAMOTOMY ABSTRACT: Following the appearance of several promising reports in the medical literature, the use of pallidotomy and thalamotomy for the treatment of Parkinson's Disease-related movement disorders has been steadily increasing over the past few years. The resurgence in these two surgical techniques can be attributed in part to the development of more reliable microlesioning systems and more accurate brain mapping techniques. Our goal is to develop a single intracranial microelectrode system that will incorporate three key components: 1.) a trimodal (i.e., recording, stimulation, lesion) microelectrode coated with biocompatible insulating materials, 2.) appropriate electronics for the control of the trimodal microelectrode, and 3.) micropositioning elements. By combining recording, stimulation and lesioning functions with biocompatible technology and materials, the trimodal microelectrode will access target brain areas with less damage to healthy tissue. Microelectrode function will be simplified by integrating each mode into a single control module. The system will Include custom-designed micropositioners. This approach will provide a degree of safety and accuracy not currently available by simplifying surgical mapping calculations and minimizing component switching error. Offering all these features in a single package will allow its pricing to be very competitive and make its clinical use more cost effective.