A simple drug used in the treatment of arthritis may provide hope for patients with blood cancer towards an affordable and effective treatment, a study has showed.
Polycythemia Vera is a type of blood cancer which causes an overproduction of red blood cells, and causes itching, headaches, weight loss, fatigue and night sweats.
The researchers from the University of Sheffield in the UK discovered that methotrexate (MTX) — a drug on the World Health Organization list of essential medicines — works by directly inhibiting the molecular pathway responsible for causing the cancer.
After initial tests carried on fruit fly cells, tests on human cells showed that MTX acts as a potent suppressor of of JAK/STAT pathway — a signalling pathway whose misregulation is central to the development of Myeloproliferative neoplasms (MPNs), the collective term for progressive blood cancers like Polycythemia Vera.
MTX was found to suppress JAK/STAT pathway activation, even in cells carrying the mutated gene responsible for MPNs in patients, the researchers noted, in the paper published in the journal Haematologica.
Importantly, the latest tests conducted on mice showed that low-dose MTX suppresses JAK/STAT pathway activity and is able to normalise both the raised blood counts and the increase in spleen size associated with the disease in these mice.
"We have now shown pretty conclusively that we can use this approach to treat mouse models of human MPNs, results which provide a much more tangible prospect of success in humans," said Martin Zeidler, from the UK varsity.
"Repurposing MTX has the potential to provide a new, molecularly targeted treatment for MPN patients within a budget accessible to healthcare systems throughout the world," Zeidler added.
MTX has been used for 35 years to treat inflammatory diseases including rheumatoid arthritis, Crohn's disease and psoriasis.
Diseases such as rheumatoid arthritis all feature inflammatory processes driven by JAK/STAT activity and the effectiveness of MTX in these inflammatory diseases may well be a consequence of its ability to dampen the JAK/STAT pathway.
The researchers now hope to conduct a full clinical trial early in 2018.