Membrane Ion-channels in Helminth Parasites: Anthelmintic Resistance and Sites of

蠕虫寄生虫中的膜离子通道：驱虫药耐药性和位点

• 批准号: 8203993
• 负责人: Richard John Martin
• 金额: $ 0.8万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8203993
• 关键词: Adult; Affect; Albendazole; American; Anthelmintics; Appearance; Area; Ascariasis; Ascaris lumbricoides; Basic Science; Benzimidazoles; Brugia malayi; Collaborations; Communication; Communities; Country; Databases; Developed Countries; Development; Development Plans; Disease; Dose; Drug Delivery Systems; Drug usage; Elephantiasis; Filaria bancrofti; Filarial Elephantiases; Filariasis; Fostering; Funding; Gated Ion Channel; Growth; Health; Helminths; Hookworms; Human; Individual; Infection; Intention; International; Intestines; Invertebrates; Ion Channel; Ivermectin; Journals; Knowledge; Lactones; Lead; Learning; Levamisole; Ligands; Location; Membrane; Minority; Modification; Monitor; Nematoda; Neurosciences; Nicotinic Agonists; Ocular Onchocerciasis; Outcome; Paper; Paralysed; Parasite resistance; Parasites; Parasitic Diseases; Parasitic infection; Parasitic nematode; Participant; Pharmaceutical Preparations; Pharmacology; Philadelphia; Physiology; Platyhelminths; Poverty; Praziquantel; Prevention; Process; Productivity; Property; Prophylactic treatment; Public Health; Publications; Published Comment; Publishing; Pyrantel; Recruitment Activity; Research; Research Personnel; Resistance; Resistance development; Sanitation; Schistosoma; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis; Scientist; Site; Societies; Soil; Therapeutic; Trichuris trichiura infection; Tropical Disease; Tropical Medicine; Vaccines; Veterinary Medicine; Work; benzimidazole; chemotherapy; disability; drug development; field study; improved; interest; knowledge base; meetings; moxidectin; neglect; novel; posters; programs; resistance mechanism; success; symposium; voltage

DESCRIPTION (provided by applicant): 'Membrane Ion-channels in Helminth Parasites: Resistance and Sites of Action for Anthelmintics' The Neglected Tropical Diseases include the Soil-Transmitted Nematode (STN) parasites (ascariasis, hookworm, and trichuriasis), filariasis (river blindness and lymphatic filariasis) and schistosomiasis. These diseases are caused by Clade I, III and V parasitic nematodes and the trematodes S. mansoni, S. haematobium and S. japonicum. Ascariasis is caused by the large intestinal roundworm, Ascaris lumbricoides. Worldwide, it occurs in 1.4 billion people. Lymphatic filariasis (elephantiasis) threatens over a billion people in 83 countries and is caused by filarial nematodes like Wuchereria bancrofti and Brugia malayi. Schistosomiasis threatens over 1 billion people and infects some 300 million individuals. These infections are both caused by, and cause, poverty. Prophylaxis and treatment of these parasitic diseases relies on the use of anthelmintic drugs because no effective vaccines are available; but, there are real concerns that mass chemotherapy will lead to development of resistance. Single-dose Mass Drug Administration [MDA] is preferable for prevention and treatment, and is used by current control and elimination programs, but is not effective with most (all) anthelmintics. The emergence of resistance to any of the drugs currently used in MDA would deal a devastating blow to the control of these debilitating diseases. No current anthelmintic has optimal properties so there is an urgent need for new lead compounds, together with a better grounding of basic science to improve the use of existing drugs and new drug development. Ion-channels in helminths are major, validated, sites of action for existing and for potential novel anthelmintics. Our conference is planned as a Pre-meeting of the American Society of Tropical Medicine, in Philadelphia at the Downtown Marriot Hotel, Dec 1-3, 2011. The symposium is timely and will facilitate spread of knowledge and foster research interest in this important and expanding area of research by our program of speakers, interactions between delegates, discussions of strategic directions and publication of the meeting's papers. There will be an open registration to national and international attendees. Our current estimated number of attendees is 100. The field is expected to be of most interest to parasitologists and public health interests. The planning and location will allow accommodation for disabilities and actively seek input and contribution from minorities. The conference will include invited expert speakers from the field and to seek submissions from interested participants to present papers and/or posters. The intention of the conference is to encourage research and knowledge of ion-channel drug targets in helminths; to encourage collaborative research; to improve recognition and support for the field of research. The planned outcome is publication of papers in a special edition of the Journal Invertebrate Neuroscience. Each speaker will review their area of expertise and be invited to comment on how the community should organize itself to advance the field of study. An important aim is to invigorate the research area and to raise the level of interest in basic research for drug development of neglected tropical diseases. We have four aims at our conference: Aim #1: To review recent progress in understanding the actions of anthelmintics at ion channels, and how resistance to those drugs can emerge. Aim #2: To publish a special issue of a learned journal summarizing current knowledge in this area. Aim #3: To encourage the formation of new cross-disciplinary international collaborations that will recruit established workers in other fields to study parasitic helminths. Aim #4: To identify and pursue opportunities for increased funding for projects in this area. The overall impact will be a powerful influence on: Odispersion and expansion of the knowledge base of membrane and ligand gated ion-channels as helminth drug targets; Oan increase in the number of active scientists supporting the field; Oidentification of strategic directions for the development of the field; O within 24 months, two or more significant (R01 or similar) proposals and two or more collaborative projects between US and international researchers will be formed. PUBLIC HEALTH RELEVANCE: Nematode parasites and flatworm parasites affect more than 1.5 billion people world- wide; these diseases are not a focus of interest in developed countries and part of a group of diseases known as the neglected tropical diseases. These helminth parasites reduce growth, health, cause lost work productivity and contribute to poverty. There are no effective vaccines and so in the absence of adequate sanitation, treatment and prophylaxis relies on anthelmintic drugs. There are concerns that Mass Drug Administration required for helminth control will produce resistance. To counter this real concern new drugs, new drug target sites and the necessary supporting basic research is required. Membrane and ligand-gated ion-channels are major, validated, anthelmintic drug target sites. The 2-day open symposium will bring together national and international experts in the field of membrane ion-channels of helminths as drug targets, will foster communication of the new knowledge base of the field, and identify strategic directions for the development of the field. It will also recruit new interest to this developing and important research topic.

描述（由申请人提供）：“蠕虫寄生虫的膜离子通道：驱虫药的耐药性和作用部位”被忽视的热带疾病包括土壤传播的线虫（线虫）寄生虫（蛔虫、钩虫和鞭虫）、丝虫病（河盲症和淋巴丝虫病）和血吸虫病。这些疾病由进化枝I、III和V寄生线虫和吸虫S引起。mansoni，S. haematobium和S.日本的蛔虫病是由大肠蛔虫引起的。在全球范围内，它发生在14亿人身上。淋巴丝虫病（象皮病）威胁着83个国家的10亿多人，由班氏吴策线虫和马来丝虫等丝虫线虫引起。血吸虫病威胁着10亿多人，感染了大约3亿人。这些感染都是由贫穷造成的，也是贫穷的原因。这些寄生虫病的预防和治疗依赖于驱虫药的使用，因为没有有效的疫苗;但是，有真实的担心，大规模化疗将导致耐药性的发展。单剂量大规模药物管理[MDA]是最好的预防和治疗，并用于目前的控制和消除计划，但不是有效的与大多数（所有）驱虫药。对目前用于MDA的任何药物的耐药性的出现将对这些使人衰弱的疾病的控制造成毁灭性打击。目前没有任何驱虫药具有最佳特性，因此迫切需要新的先导化合物，以及更好的基础科学，以改善现有药物的使用和新药开发。蠕虫中的离子通道是现有和潜在的新型驱虫剂的主要、经验证的作用位点。我们的会议计划作为美国热带医学会的预备会议，在费城市中心的Albertot酒店，2011年12月1日至3日。研讨会是及时的，将促进知识的传播，并通过我们的演讲者计划，代表之间的互动，战略方向的讨论和会议文件的出版，培养对这一重要和不断扩大的研究领域的研究兴趣。将对国内和国际与会者开放注册。我们目前的估计出席人数为100人。该领域预计将是最感兴趣的寄生虫学家和公共卫生利益。规划和地点将允许残疾人住宿，并积极寻求少数群体的投入和贡献。会议将邀请该领域的专家发言，并征求感兴趣的与会者提交文件和/或海报。会议的目的是鼓励研究和蠕虫离子通道药物靶点的知识;鼓励合作研究;提高对研究领域的认可和支持。计划的成果是在《无脊椎动物神经科学》杂志的特刊上发表论文。每位演讲者将回顾他们的专业领域，并应邀就社区应如何组织起来推进研究领域发表评论。一个重要的目标是振兴研究领域，提高人们对被忽视的热带疾病药物开发基础研究的兴趣。我们在会议上有四个目标：目标1：回顾最近在了解驱虫药在离子通道中的作用方面的进展，以及对这些药物的耐药性如何出现。目标2：出版一份学术期刊特刊，总结这一领域的现有知识。目标3：鼓励形成新的跨学科国际合作，将招募其他领域的工作人员来研究寄生蠕虫。目标4：确定和寻求增加这一领域项目资金的机会。总体影响将是：传播和扩大作为蠕虫药物靶点的膜和配体门控离子通道的知识基础;增加支持该领域的活跃科学家人数;确定该领域发展的战略方向; O在24个月内，将形成两个或两个以上的重大（R 01或类似）提案，以及美国和国际研究人员之间的两个或两个以上的合作项目。 公共卫生关系：线虫寄生虫和扁形虫寄生虫影响全世界15亿多人;这些疾病在发达国家不是关注的焦点，而是被称为被忽视的热带病的一组疾病的一部分。这些蠕虫寄生虫降低生长，健康，导致工作生产力下降，并导致贫困。没有有效的疫苗，因此在缺乏适当卫生条件的情况下，治疗和预防依赖于驱虫药物。有人担心，大规模药物管理所需的蠕虫控制将产生耐药性。为了解决这一真实的问题，需要新的药物、新的药物靶点和必要的支持性基础研究。膜和配体门控离子通道是主要的、经验证的驱虫药物靶位点。为期两天的公开研讨会将汇集作为药物靶点的蠕虫膜离子通道领域的国内和国际专家，促进该领域新知识基础的交流，并确定该领域发展的战略方向。它也将为这一发展中的重要研究课题带来新的兴趣。