Monoclonal Antibodies to GABA Metabolic Pathway Proteins

描述(申请人提供)：全面研究控制神经递质GABA代谢的蛋白质的功能和相互关系，不仅对于了解神经元信号的基本生物学，而且对于发现许多严重神经疾病的潜在新疗法都是重要的。由于目前缺乏针对这些分子的特定研究试剂，特别是识别控制GABA合成、传递和处置的关键酶的单抗，这一研究一直受到阻碍。为了满足这些需求，我们打算产生这种抗体，并在关键的实验室操作中优化它们的使用。这些目标将通过抗原生产、免疫、杂交瘤融合和抗体筛选以及在多种实验室技术中对产生的抗体进行严格测试的计划来实现。在这项提案和后续的第二阶段提案中产生的抗体将作为研究基础生物学的可用实验室试剂为研究界服务，但也将以两种方式为新疗法的开发做出贡献：第一，直接通过它们作为新型治疗剂的潜在用途，第二，通过它们在实验室的使用将允许的新发现。

DESCRIPTION (provided by applicant): Comprehensive study of the function and interrelationships of the proteins controlling the metabolism of the neurotransmitter GABA is important not only for understanding the basic biology of neuronal signaling, but also for uncovering potential new therapies for many severe neurological disorders. Such study has been hampered by the current lack of specific research reagents targeting such molecules, in particular monoclonal antibodies that recognize key enzymes controlling the synthesis, delivery, and disposition of GABA. To address these needs, we intend to generate such antibodies and optimize their use in critical laboratory manipulations. These goals will be met through a program of antigen production, immunization, hybridoma fusion and antibody screening, and rigorous testing of generated antibodies in multiple laboratory techniques. The antibodies produced in this proposal, and in a follow-on phase II proposal, will serve the research community as available laboratory reagents to study basic biology, but will also contribute to novel therapy development in two ways: first, directly through their potential use as novel therapeutic agents, and second, through the new discoveries their laboratory use will allow.