DEVELOPMENT OF NEW ANTISEIZURE DRUGS FROM PHENOLS

DESCRIPTION: (Applicant's Abstract) The objective of this project is to synthesize new anti-seizure medications based on certain naturally occurring phenols. Pharmacognetics isolated a naturally occurring phenol derivative from a plant which had historically been used to treat seizures. This compound and several related naturally occurring compounds have shown significant anti-seizure activity. There is evidence that modification of these naturally occurring compounds yields more potent anti-seizure compounds that are virtually devoid of side effects in rodent testing. Pharmacognetics plans to (1) synthesize analogs of substituted phenols with known anti-seizure activity as well as several closely related compounds; (2) test these compounds for anti-seizure activity, adverse effects and toxicity; and (3) further explore structure-activity relationships and mechanisms of these compounds. The goal of this Phase I proposal is to synthesize one or more lead compounds which maximize anti-seizure potency while minimizing adverse effects. $ = 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 510 --PROJECT NUMBER......1 R43 NS37272-01 INVESTIGATOR NAME/ADDRESS FY 97 CHUNG, SHAN IRG/INTRAMURAL UNIT..ZRG2 PEPTIMMUNE, INC. AWARD AMOUNT......... $99,999 840 MEMORIAL DR CAMBRIDGE, MA 02139 PERFORMING ORGANIZATION: PEPTIMMUNE, INC. TITLE PEPTIMERS TM--IMMUNOTHERAPY FOR AUTOIMMUNE DISEASE ABSTRACT: DESCRIPTION: (Adapted from the applicant's abstract) Peptide epitopes of autoantigens make attractive candidates for immunotherapy of autoimmune diseases because of their potential to specifically suppress autoimmune reactions. Recently, "peptide oligomers," peptide epitopes alternating with a peptide spacer of fixed length, have been shown to dramatically enhance immunopotency compared to their monomeric counterparts. We propose to utilize such peptide oligomers (Peptimers(TM)) as the basis of a novel, antigen- specific approach to the treatment of autoimmune diseases. Our initial experiments will address the production and in vitro testing of purified peptide oligomers composed of myelin basic protein (MBP) amino acid residues 84-102 and proteolipid protein amino acid residues 139-151. The former has been implicated in multiple sclerosis (MS) and the latter has been used to induce a chronic form of experimental allergic encephalomyelitis (EAE; an animal model of MS) in rodents. Peptide oligomers from 4- to 28- epitopes, joined by peptide spacers, will be tested for their potential to induce tolerance as demonstrated by in vitro assays using T-cell clones isolated from MS patients and from rodents with EAE. $ = 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 511 --PROJECT NUMBER......1 R43 NS37523-01 INVESTIGATOR NAME/ADDRESS FY 97 SARACIONE, JOSEPH IRG/INTRAMURAL UNIT..ZRG1 CARTESIAN RESEARCH, INC AWARD AMOUNT......... $98,984 PO BOX 372, 37550 RUBEN LN-STE SANDY, OR 97055 PERFORMING ORGANIZATION: CARTESIAN RESEARCH, INC. TITLE IMPROVED STEREOTAXIC INSTRUMENTATION AND METHODOLOGIES ABSTRACT: DESCRIPTION (Investigator's Abstract): Many procedures in experimental neuroscience depend upon accurate and precise surgical access to specific structures in the brain, in reference to known landmarks on the skull and three-dimensional information about brain structures as published in stereotaxic atlases. The current stereotaxic instrument has seen little change from the date of its original design, about 35 years ago. In the meantime, the machine tool industry has seen dramatic advances in the accuracy and precision of basic mechanical mechanisms. The purpose of this project is to determine the accuracy and precision that might be obtained with a stereotaxic instrument that has been completely re-designed using modern machine tool principles. This new design includes a precision surface plate which provides a reliable planar datum. Second, a new universal manipulator will be developed using precision linear scales and digital readouts with a resolution of 1 micron. Finally, an automatic indexing tool holder will allow the user to interchange centering scopes, drills, and electrode holders on a common vertical axis. This instrument is expected to improve the accuracy of stereotaxic surgery by a factor of 5- to 20-fold; these results will be verified by an independent calibration laboratory accredited by the NIST. $ = 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 512 --PROJECT NUMBER......1 R43 RR09811-01A3 INVESTIGATOR NAME/ADDRESS FY 97 ZIARATI, MOKHTAR IRG/INTRAMURAL UNIT..ZRG7 RESONANCE TECHNOLOGY COMPANY AWARD AMOUNT......... $91,954 16525 SHERMAN WAY, SUITE C-2 VAN NUYS, CA 91406 PERFORMING ORGANIZATION: RESONANCE TECHNOLOGY CO. TITLE 3D MRI COMPATIBLE VIDEO SYSTEM ABSTRACT: Resonance Technology, Inc. has become the leading manufacturer of patient comfort systems for Magnetic Resonance Imaging (MRI). We propose to develop a new generation of video displays, called the "VR-Vision" providing a virtual reality-like environment, including a wide, adjustable, field of view, high resolution 3D display and high quality sound system to limit the patient's awareness of the scanning environment. The integration of eye tracking and patient response keypads extends the capabilities of this unit to clinical neurological and neuroscientific research uses. Our prototypes have overcome the important technical limitations of eliminating electrical noise that might otherwise compromise image quality, and we have protected the device from the large static and time- varying magnetic fields. Our instruments differ greatly from our competition in offering greater resolution, convenience and reliability, better matching of individual focal lengths and interpupillary distance and, in our proposed devices, integral infrared eye tracking and a patient/subject response device. Early inquiries and pre-sales indicate substantial customer interest in the product.