A new clinical trial to improve the quality of life of people with myelodysplastic syndromes
The study, based on a 2023 scientific publication by the team in Science Translational Medicine, will test whether a high dose of vitamin B5 can help reduce severe anemia in patients with myelodysplastic syndromes carrying a mutation in the SF3B1 gene.
“We want to see if we can reduce the need for transfusions and give people more independence in their daily lives. If successful, this could open the door to a more accessible treatment option for patients who currently have very few choices,” explains Dr. Kevin Rouault-Pierre.
This funding marks an important step in advancing research and translating it into concrete benefits for patients. This phase II clinical trial will recruit around 30 patients over 5 years in England, at centers in Birmingham, Oxford, London, Manchester, and in Scotland.
Management context of myelodysplastic syndromes
Low-risk myelodysplastic syndromes (MDS) represent a major and persistent clinical need. Patients frequently present with chronic cytopenias, often requiring transfusions for many years, with few therapeutic options capable of durably modifying disease progression. Despite advances, mechanism-based therapeutic approaches remain strikingly limited.
MDS are stem cell disorders. A central biological feature of low-risk MDS is the high prevalence (>50%) of mutations affecting essential RNA splicing factors, including SF3B1, SRSF2, U2AF1, and ZRSR2. These mutations arise early during clonal evolution and profoundly shape both disease biology and its clinical manifestations.
Splicing alterations lead to the production of thousands of aberrant transcripts, either eliminated through nonsense-mediated decay (NMD) or translated into truncated or dysfunctional proteins. This chronic production imposes sustained stress on RNA and protein quality control pathways. Our laboratory has contributed to characterizing this pathological landscape and has recently demonstrated that aberrant splicing of coenzyme A synthase (COASY) is a direct determinant of ineffective erythropoiesis in SF3B1-mutant MDS. Remarkably, this defect is reversible through targeted metabolic intervention using vitamin B5 or succinyl-CoA.