The 2007 Progeria Research Foundation Workshop on Hutchinson Gilford Progeria

描述(由申请人提供)： Hutchinson-Gilford早衰症(HGPS或Progeria)是一种罕见的、致命的早衰疾病，所有早衰症儿童平均13岁死于中风或心脏病发作，这是长期动脉粥样硬化的结果。早衰症和其他一些程序性疾病是由编码层蛋白A的LMNA基因突变引起的，层蛋白A是一种内核膜蛋白，是全身关键的结构和细胞信号分子。2003年，Lamin A基因在早衰症中作用的转折点的发现为新的早衰症小鼠模型的开发和针对早衰症儿童的首次药物试验(第二阶段)提供了框架。重要的是，在正常成年人中新发现的孕激素突变蛋白(孕激素)的产生被认为是心血管疾病(CVD)和典型衰老过程中的一个潜在因素。 早衰症研究基金会(PRF)成立于1999年，其使命是通过研究和教育，发现早衰症及其衰老相关疾病的病因、治疗和治愈。PRF和NIH的合作努力通过每隔一年举办一次的研讨会：2001年、2003年和2005年，对早衰症及其与心血管疾病和老龄化的关系进行了令人兴奋的科学研究。前三次研讨会推动了早衰症领域取得了令人振奋的科学进步。为了保持科学发现的势头和对早衰症医学界的支持计划，PRF正在为2007年的研讨会(11月12-14日，马萨诸塞州波士顿)寻求NIH资金。 2007年的研讨会议程是由一个由老龄化、板层生物学和老年病领域的国家专家组成的咨询小组指导的PRF组织委员会制定的。研讨会的结构将包括22位正式演讲者，2次“最新”实验结果的公开会议，30-40幅海报演示，以及与早衰症儿童及其家人见面的机会。在现场分享餐饮和海报会议期间，将鼓励非正式讨论。鼓励初级科学家参与并分享他们的成果，特别是通过海报会议。选定的演讲者(临床医生和科学家)在各自领域做出了重大贡献，涵盖了遗传学、生理学、细胞生物学、生物化学、心血管疾病和衰老等领域。研讨会的形式旨在促进合作的科学努力，讨论资金来源，为确定新的研究方向提供一个开放的论坛，并向与会者通报正在进行的帮助科学和医学界的PRF基础设施计划的进展情况(即PRF患者登记、细胞和组织库、临床和研究数据库以及诊断计划)。我们正处于研究由层蛋白变化引起的疾病机制的新方向的早期阶段。探索这种分子的基本细胞生物学和生物化学将需要科学界的密集研究和合作努力。我们预测，2007年研讨会的一个亮点将是讨论法尼基转移酶抑制剂在早衰症动物模型中的有效治疗，以及可能用于早衰症儿童的治疗。研讨会的主题将包括这种多系统疾病的自然历史，遗传疗法的潜力，以及HGPS中的干细胞移植。早衰症突变对模型小鼠不同组织的影响可能会推动对心脏病和正常衰老的研究，以及关于骨质疏松症、胰岛素抵抗和早衰症所发现的其他发育异常发生机制的重要研究。(摘要结束)

DESCRIPTION (Provided by applicant): Hutchinson-Gilford progeria syndrome (HGPS or Progeria) is a rare, fatal, premature-aging disease in which all Progeria children die at an average age of thirteen years due to strokes or heart attacks, a consequence of prolonged atherosclerosis. Progeria and a number of other progeroid diseases are caused by a mutation in the LMNA gene which encodes lamin A, an inner nuclear membrane protein that serves as a key structural and cell signaling molecule throughout the body. The turning-point discovery in 2003 of the lamin A gene's role in Progeria has provided the framework for the development of new mouse models of Progeria and a first-ever drug trial (phase II) for Progeria children. Importantly, the newly discovered production of the Progeria mutant protein (progerin) in the normal adult population is thought to be a potential factor in the development of cardiovascular disease (CVD) and in the typical aging process. The Progeria Research Foundation (PRF) was founded in 1999 with the mission to discover the cause, treatment and cure for Progeria and its aging-related disorders, through research and education. The collaborative efforts of PRF and NIH has yielded exciting scientific research into Progeria and its relationship to CVD and aging through a series of workshops held every other year: 2001, 2003 and 2005. These prior three workshops have propelled the field of Progeria into exciting scientific advances. To maintain the momentum of scientific discovery and support programs for the Progeria medical community, PRF is seeking NIH funding for a 2007 workshop (Nov 12-14, Boston MA). The 2007 workshop agenda has been formed by a PRF organizing committee with the guidance of an advisory panel of national experts from the fields of aging, lamin biology, and Progeria. The structure of the workshop will include 22 formal speakers, 2 open sessions for "latebreaking" experimental results, 30-40 poster presentations, and an opportunity to meet Progeria children and their families. Informal discussions will be encouraged during on-site shared meals and poster sessions. Junior scientists are encouraged to participate and share their results, particularly through the poster sessions. The selected speakers (clinicians and scientists) have made significant contributions in their fields, encompassing areas of genetics, physiology, cell biology, biochemistry, CVD and aging. The workshop format has been designed to foster collaborative scientific efforts, discuss funding sources, provide an open forum for determining new directions for research, and inform participants on the progress of ongoing PRF infrastructural programs that aid the scientific and medical communities (i.e. PRF Progeria patient registry, cell and tissue bank, clinical and research database, and diagnostics program). We are at the early stages of new directions for research into the mechanisms of disease caused by alterations in the lamin protein. Exploration into the basic cellular biology and biochemistry of this molecule will require intense study and collaborative efforts from the scientific community. We predict a highlight of the 2007 workshop will be the discussion of farnesyltransferase inhibitors as effective treatment in Progeria animal models and potentially in children with Progeria. Workshop topics will include the natural history of this multi-system disease, the potential for genetic therapies, and stem cell transplantation in HGPS. Effects of Progeria mutations on different tissues of model mice are likely to fuel studies on heart disease and normal aging, as well as important studies on the mechanisms by which osteoporosis, insulin resistance, and other developmental abnormalities found in Progeria arise. (End of Abstract)