One of the major challenges in developing treatments for rare diseases is that, though we generally have a very good description of the health issues the patient faces, it is often the case that there is very limited information as to why the patient presents with these issues.
For Diamond-Blackfan anemia the prominent effect, the loss of red blood cell production, is eminently obvious, and though we know the cause, mutations in ribosomal protein genes, the actual mechanistic defect that causes specific red blood cell loss remains unclear. The result is this is that it is extraordinarily difficult to develop new treatments, as the problem itself is not precisely defined.
Our goal is to better understand the intricacies of DBA, with the hope that we may reveal a deeper understanding of the biology behind the disease, in turn allowing us to employ existing treatments or to develop altogether novel treatments. To facilitate this we take advantage of a peculiarity of the Marte family. Boris carries the mutation that causes DBA, but is not anemic. We have established stem cell lines derived from the family, as well as primary stem cells taken from blood to search out the difference between Boris and the children. We are then able to promote red blood cell formation in a controlled laboratory setting to allow for in depth analyses. By comparing cells from Boris with those from the children we may be able to spot the reason why Boris in unaffected. So far, our work has already revealed unexpected outcomes, which allowed us to posit a novel potential biological mechanism for DBA. We have now established two methods for testing potential DBA treatments, and are in the process of investigating both existing and novel therapeutics we are developing. Additionally, we are in the early stages of developing a potential prognostic test for DBA.
Beyond our initial goal, understanding the biological problem behind DBA will also reveal new insight into how red blood cells are formed in healthy individuals. Novel findings may also shed light on other blood based diseases. While it will take some time, we are optimistic that this work will impart a positive impact on the lives of people with DBA. Medical research is often depicted as a process catalyzed with big breakthroughs or eureka moments, but the reality is that progress is made in a series of small steps that build upon each other. Here we are following in the footsteps in decades of work before us, providing a trailhead for the future.
Devon Germain, Researcher at Max Perutz Labs / Medical University Vienna, June 2021