Hemophilia is a genetic disorder of blood coagulation affecting approximately 17,000 individuals in the United States. The two most common 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. Three human trials are now underway, two of which employ viral vectors; the third is an ex vivo, nonviral study. A number of research questions remain unanswered, and progress in the field is facilitated by holding regulaily-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 April 19-21, 2001 at The Salk Institute for Biological Studies in La Jolla. California. The last workshop in March of 2000 looked at a number of questions related to immune responses to various viral vectors and transgenes, and a special pre-workshop summit will focus on the circumvention of such immune responses. Other 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 and HIV infection and treatment on gene therapy; and ethical concerns in the use of human subjects, including clarification of patient and physician rights and responsibilities. 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.
