Halfway through our six-year research project, we recently held a meeting with all participating scientists and the user committee to share the status at this midpoint. The various groups provided an overview of their progress, and new plans were discussed.
Below, you will find a more detailed summary of the key topics that were addressed.
TRACER: treating hereditary anemias through stem cell research
ZonMw PSIDER consortium TRACER 10250022110001
The TRACER consortium, funded by the ZonMw PSIDER program, studies hereditary anemias such as sickle cell disease (SCD) and Diamond-Blackfan Anemia Syndrome (DBAS). In hereditary anemias, the formation of healthy red blood cells from hematopoietic stem cells is disrupted. TRACER cell biologists will use induced pluripotent stem cells (iPS cells) derived from patients to study disease mechanisms and create genetically repaired, patient-specific red blood cells and hematopoietic stem cells. This will enable TRACER clinicians to develop better treatments. Additionally, the ethical and societal aspects for patients, clinicians, and policymakers are being explored. The new treatments must meet the 4A framework: Acceptability, Availability, Accessibility, and Affordability.
The research conducted by the ZonMw PSIDER TRACER consortium is now (December 2024) halfway through its six-year duration. What has been achieved in the first three years?
In laboratory research, significant progress has been made on several critical points:
Creating iPS cells from patients with SCD and DBAS.
Producing red blood cells from the iPS cells of patients.
Establishing that red blood cells from iPS cells provide a good disease model for DBAS.
Correcting the genetic defects in some of these iPS cells: the SCD mutation and one of the DBAS mutations have now been successfully repaired.
Developing scalable cultures for iPS cells and directing the formation of hematopoietic cells.
Adapting these protocols for use in bioreactors.
Thanks to external developments, including the publication of two independent studies (1, 2) describing that blood stem cells can be made from iPS cells, TRACER has the wind at its back. This was one of the riskiest aspects of the TRACER project. The TRACER consortium has responded by intensifying efforts in iPS cell culture, genetic correction of iPS cells, and developing iPS cells that allow the formation of hematopoietic stem cells to be observed under the microscope.
From TRACER’s research on responsible research & innovation (RRI), it has been found that, on the one hand, patients have a strong need for new therapies and are willing to use them. On the other hand, there are significant gaps in knowledge transfer, not only to patients but also within the medical sector. Economic considerations also play a significant role. The approval by regulatory authorities of Casgevy, a new genetic therapy for SCD patients, received widespread publicity. However, the question remains as to when an SCD patient in the Netherlands will be treated with it. This therapy is expected to cost at least 2 million euros per patient. For this reason, TRACER researchers are taking these RRI aspects into account at an early stage and are actively involved in initiatives to develop more accessible alternatives for such advanced treatments in the Netherlands.
Building on these developments, TRACER’s RRI researchers began working with the 4A framework in 2024 for SCD and DBAS. The 4 A’s stand for Acceptability, Availability, Accessibility, and Affordability of advanced treatments. In addition to an extensive literature analysis, interviews were conducted with patients and families. These interviews are extremely valuable because they provide deeper insights into the experiences of these patients and their families, as well as the choices they make. The interviews are currently being analyzed. Should more families be open to sharing their experiences and opinions, they can contact Lou van Hooff for more information.
Finally, we are incredibly proud of TRACER researcher Gerald de Haan from Sanquin, who recently received a multimillion-euro grant from the European Research Council. This ensures the long-term future of research into the formation of hematopoietic stem cells from iPS cells. Congratulations to Gerald de Haan and his laboratory team, including Arthur Svendsen, Edurne Solabarrieta Larrañaga, Liza Dijkhuis, and Helena Kooi. It is fantastic to see their hard work and unwavering dedication to finding new treatments for patients who rely on blood transfusions and stem cell transplants being recognized internationally!
Text, Dec. 2024, Sjaak Philipsen, TRACER Coordinator
