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.
