NHF Fifth Workshop on Gene Therapies for Hemophilia

描述（由申请人提供）：血友病是一种血液凝固的遗传性疾病，在美国影响约17,000人。血友病的两种最常见的形式是血友病A和血友病B，分别由凝血因子VIII和IX的缺陷或缺乏引起。虽然治疗对许多血友病患者是有效的，但它包括在出血事件期间或之后终身静脉输注凝血因子。这种疗法有许多缺点，因此基因疗法已被研究作为治疗血友病的一种手段。血友病是最可能接受基因治疗的遗传疾病之一，因为它是由单个基因的缺陷引起的。血友病的基因治疗将功能凝血因子基因转移到血友病患者的细胞中，使患者的身体能够制造凝血因子蛋白。利用各种病毒载体在动物体内获得持续表达凝血因子的临床前研究已经取得了相当大的成功。几项人体试验目前正在进行或已经完成。除了一个，其他的都使用了病毒载体。许多研究问题仍然没有答案，通过定期召开研讨会，研究人员可以讨论他们工作的现状，促进了该领域的进展。国家血友病基金会提议在2002年4月再举办一次基因治疗系列研讨会。2000年3月和2001年4月的最后一次研讨会研究了许多与免疫反应有关的问题对各种病毒载体和转基因。对病媒的先天免疫已成为安全的重要决定因素，并将在研讨会上更深入地讨论。其他亟待解决的问题包括确定转基因表达的最佳靶组织；基因治疗再治疗的安全性；与每个病媒系统相关的风险；丙型肝炎感染及治疗对基因治疗的影响；以及使用人体受试者的伦理问题，包括澄清患者和医生的权利和责任。重要的是，基因疗法治疗血友病的替代方案将得到解决，如改进的蛋白质、基于细胞的疗法和口服生物活性分子。随着人体临床试验的进行，该研讨会为基础研究人员、临床医生、联邦监管机构、制药公司代表和出血性疾病社区成员之间的公开交流和辩论提供了一个至关重要的机会。

DESCRIPTION (provided by applicant): Hemophilia is a genetic disorder of blood coagulation affecting approximately 17,000 individuals in the United States. The two most commons forms of hemophilia are hemophilia A and hemophilia B, caused by defects or deficiencies in clotting factors VIII and IX, respectively. While treatment is effective for many people with hemophilia, it consists of life-long, intravenous infusions with clotting factor administered during or after a bleeding event. This therapy has many drawbacks, and thus gene therapy has been investigated as a means of curing hemophilia. Hemophilia is among those genetic disorders most likely to be amenable to gene therapy because it results from defects within single genes. Gene therapy for hemophilia would transfer functioning clotting factor genes into cells in a person with hemophilia, enabling that individual's body to manufacture clotting factor proteins. There has been considerable success in pre-clinical studies in using various viral vectors to obtain sustained expression of clotting factor in animals. Several human trials are now underway or have been completed. All except one employ viral vectors. A number of research questions remain unanswered, and progress in the field is facilitated by holding regularly convened workshops where investigators can discuss the current state of their work. The National Hemophilia Foundation proposes to hold another in a series of gene therapy workshops in April 2002. The last workshops in March of 2000 and April of 2001 looked at a number of questions related to immune responses to various viral vectors and transgenes. Innate immunity to vectors has emerged as an important determinant of safety, and will be addressed in more depth in the workshop. Other emergent concerns to be addressed include identification of the best target tissues for transgene expression; the safety of gene therapy retreatment; the risks associated with each vector system; the effect of hepatitis C infection and treatment on gene therapy; and ethical concerns in the use of human subjects, including clarification of patient and physician rights and responsibilities. Importantly, alternatives to gene therapy to cure hemophilia will be addressed, such as improved proteins, cell-based therapy, and oral delivery of bioactive molecules. The workshop affords a critically important opportunity for open communication and debate among basic researchers, clinicians, federal regulators, representatives of pharmaceutical companies, and members of the bleeding disorders community as human clinical trials proceed.