Inhaled dopamine agonists for late stage Parkinsonism

吸入多巴胺激动剂治疗晚期帕金森病

• 批准号: 6792448
• 负责人: Patrik Munzar
• 金额: $ 80.36万
• 依托单位: ALEXZA MOLECULAR DELIVERY CORPORATION
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6792448
• 关键词: Parkinson' s disease; Saimiri; antiparkinson drugs; biomedical equipment development; biomedical equipment safety; brain disorder chemotherapy; dogs; dopamine agonists; drug delivery systems; drug screening /evaluation; inhalation drug administration; medical complication; miniature biomedical equipment; neuromuscular disorder; nonhuman therapy evaluation; portable biomedical equipment; self care

DESCRIPTION (provided by applicant): Many patients in the later stages of Parkinson's disease experience periods of acute immobility ("off' periods) that substantially decrease their quality of life. The most effective pharmacological treatments for these acute "off' periods are dopamine agonist drugs, which can rapidly abort "off' periods if delivered quickly into the blood stream via injection. The utility of this form of treatment is, however, limited due to its invasiveness and the inability of many late-stage Parkinson's disease patients to self-administer injections. The aim of this project is to develop an inhalation device that delivers dopamine agonists rapidly into the blood stream in a convenient, non-invasive fashion. We have developed a novel drug delivery technology that involves heating drugs such that they vaporize, but do not degrade, and subsequently cool and condense into small particle aerosols suitable for systemic delivery by inhalation. In Phase I of this proposal, we have constructed a handheld device capable of generating pure aerosols of several dopamine agonists, demonstrated the biological activity of these aerosols in vitro, and confirmed that the aerosol's particle size is appropriate for systemic delivery via deep lung inhalation. In Phase II of this grant we will prove that inhaled dopamine agonists rapidly reverse Parkinson's disease symptoms in an animal model and will conduct all pre-clinical work required to initiate clinical development of inhaled dopamine agonist for treatment of late stage Parkinson's disease. Successful completion of these aims will allow us to move into Phase I clinical testing, which will be funded by a combination of outside investors, FDA funds for the development of orphan drugs, and/or a partnership with a major pharmaceutical company. Eventual FDA approval of inhaled dopamine agonist product for treatment of motor fluctuations in late stage Parkinson's will substantially improve the treatment of this serious and common neurodegenerative disease.

描述（由申请人提供）：在帕金森氏病经历急性不动的后期，许多患者大大降低了他们的生活质量。这些急性的最有效的药理治疗方法是多巴胺激动剂药物是多巴胺激动剂药物，可以快速降级到该形式的疾病中，这可以使其迅速降级到限制性的效果。许多晚期帕金森氏病的患者无法自我注射。吸入。在该提案的第一阶段，我们构建了一种能够生成几种多巴胺激动剂的纯净气溶胶，证明了这些气溶胶在体外的生物学活性，并证实了气溶胶的粒径适合于该赠款的全身性驱动器。动物模型并将进行所有临床前的工作，以启动吸入多巴胺激动剂的临床发展，以治疗帕金森氏病的后期，这将使我们能够进入I期临床测试，这将由外部投资者的组合提供，以便于晚期帕金森氏症治疗运动波动的多巴胺激动剂产物将大大改善这种严重和常见的神经退行性疾病的治疗。