Researchers have discovered that vitamin B5 in combination with existing drugs may be the key to improving outcomes in patients with myelodysplastic syndromes (MDS) and ineffective red blood cell production, according to a novel study published by Mian et al in Science Translational Medicine.
Background
MDS is a type of blood cancer characterized by a stem cell disorder where the production of healthy red blood cells is disrupted. Currently, there are no curative treatments for patients with MDS, but some medications may help slow the progression of the disease.
Patients with MDS often go on to develop acute myeloid leukemia (AML), and around 50% of patients become resistant to existing treatments for MDS within 18 months to 2 years of treatment. These patients are heavily reliant on red blood cell transfusions—which can be painful and dangerous as a result of the iron overload in the bloodstream. The researchers stressed that because treatment options are limited for these patients, it is imperative to uncover new ways to treat MDS and prevent its progression to AML.
Study Methods and Results
In thee new study, the researchers analyzed blood samples from 42 patients with MDS and found that the bifunctional enzyme COASY may be critical in regulating red blood cell production in the bone marrow. Partial loss of the COASY enzyme in patients with MDS may severely disrupt red blood cell production and cause anemia.
Additionally, when the researchers tested whether they could boost red blood cell production with vitamin B5 supplementation or the metabolite succinyl-CoA, they found that these treatments increased the maturation of red blood cells.
“Current treatments for MDS are often associated with [a] reduced quality of life as well as [an] increased risk of progression to [AML]. Understanding the biology behind this stem cell disorder is key to unlocking new treatments of the future,” emphasized senior study author Kevin Rouault-Pierre, BSc, MSc, PhD, Group Leader at the Barts Cancer Institute at the Queen Mary University of London. “Our next steps will be to further investigate how to boost red blood cell production and work toward testing new treatments in clinical trials,” he added.
“Given [that] our elderly population is increasing and age is the dominant risk factor for the development of MDS, we will start to see more and more people with this type of blood cancer,” explained lead study author Syed Mian, BSc, PhD, a postdoctoral research fellow in the Hematopoietic Stem Cell Laboratory at The Francis Crick Institute. “Anemia-related symptoms such as chronic fatigue are commonly reported in MDS, and the current red blood cell transfusions—although essential—come with potential complications and also require substantial human and financial resources. Therefore, it’s essential that we find alternative ways to regulate long-term red blood cell production in these patients. Our results may also potentially help with [the] treatments of other diseases where patients commonly present with anemia,” he concluded.
The researchers highlighted that their findings uncovered the potential for COASY metabolites to treat anemia in patients with MDS, and hope to further study the key role that the COASY pathway plays in red blood cell maturation.
Disclosure: For full disclosures of the study authors, visit science.org.
