From restoring clotting to rethinking cure: An ethical exploration of gene therapy for hemophilia

Since the emergence of gene therapy research in the 1990s, people with hemophilia and their healthcare providers have hoped that this innovation might one day provide a cure. Hemophilia, caused by a deficiency of clotting factor VIII (hemophilia A) or IX (hemophilia B), leads to spontaneous or trauma-induced bleeding into muscles and joints. Current treatments, including regular intravenous infusions of clotting factor concentrates or subcutaneous administration of emicizumab, have allowed individuals in resource-rich settings, such as the Netherlands, to achieve near-normal life expectancy and quality of life. However, gene therapy also raises ethical questions.
Thereforem this thesis investigates how gene therapy for hemophilia can be further developed and implemented in an ethically responsible manner, responsive to the needs of stakeholders. It focuses on two research questions: what are the ethically relevant aspects of gene therapy for hemophilia, and what does it mean to “cure” the condition?
Based on a literature review, we constructed three ethical themes: living up to expectations, psychosocial impacts, and costs and access. While patients often view gene therapy as a permanent cure that will overcome the burdens of current treatment, the reality thus far has been more complex. Participants in early trials have faced new challenges, including the need for immunosuppressive therapy and uncertain long-term efficacy. The psychosocial dimension involves the potential impact of gene therapy on personal identity and the need for support in adjusting to new health states or declining therapeutic effects. The third theme, costs and access, highlights the high price of gene therapy and its implications for equitable availability. The review concludes that narratives surrounding gene therapy should shift from framing gene therapy as a cure to presenting it as one among several temporary treatment options.
Three further ethical themes were identified via interviews with people with hemophilia, parents of children with hemophilia, healthcare professionals, and other stakeholders: freedom and independence, trust and altruism, and incremental benefits. Gene therapy was associated with hopes for greater independence, yet participants also expressed concerns about new dependencies and risky behaviors. The second theme describes the high level of trust that people with hemophilia have in their physician and in research, as a result of which they were very willing to participate in research. Third, respondents questioned whether gene therapy provides sufficient advantages over current therapies, given its risks and uncertainties.
The thesis also explored the concept of “cure,” a central yet ambiguous term in gene therapy discourse. The analyses demonstrated that “cure” can refer to normalization of the body, obtaining a normal life, or change in narrative identity. Given these variations, the term should be used cautiously and context-specifically to prevent misunderstanding and unrealistic expectations.
I end with three concrete recommendations for the further development of gene therapy and hemophilia care in general: to reflect on the goals of gene therapy, to have attention for the ethics of communicating about gene therapy and to design care for hemophilia in a way that can enhance the independence of people living with hemophilia.