Arthritis Drug can Treat Rare Type of Blood Cancer

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Highlights:

• A drug used to treat arthritis can be used to treat blood cancer, finds a study by a research team at the University of Sheffield
• Polycythemia Vera is a type of blood cancer that affects 3,000 people a year
• Arthritis drug could be an affordable and effective treatment for patients with blood cancer

Polycythemia Vera is a rare type of blood cancer, which causes an overproduction of Red Blood Cells (RBCs). Currently, available treatments for Polycythemia Vera do not slow the disease progression. A research team at the University of Sheffield has discovered that a commonly used arthritis drug can effectively treat blood cancer.

Arthritis Drug can Treat Rare Type of Blood Cancer

Methotrexate (MTX) is a drug commonly used to treat arthritis which is also on the World Health Organization list of essential medicines. MTX works by directly inhibiting the molecular pathway responsible for causing disease.

‘Patients with a rare type of blood cancer called Polycythemia Vera can be effectively treated with a commonly used arthritis drug, methotrexate (MTX).’

Dr Martin Zeidler, from the University of Sheffield's Department of Biomedical Science, along with colleagues from the Department of Hematology at the Royal Hallamshire Hospital conducted the study. The study was funded by the Medical Research Council (MRC).

Initially, tests were carried out on fruit fly cells to screen for molecules that modulate JAK/STAT signaling.

In humans, the misregulation of JAK/STAT signaling pathway is central to the development of Myeloproliferative neoplasms (MPNs), which is the collective term for progressive blood cancers like Polycythemia Vera.

Tests carried out on human cells showed that the drug MTX acts as a potent suppressor of JAK/STAT pathway activation. The drug suppressed the JAK/STAT pathway activation even in cells carrying the mutated gene responsible for Myeloproliferative neoplasms in patients.

The research team also conducted tests on mice to see the effect of the drug MTX in suppressing JAK/STAT pathway activation. Dr Zeidler, said, that the tests on mice were entirely consistent with the cell-based studies.

The findings showed that low-dose MTX suppressed JAK/STAT pathway activation. It also normalizes both the raised blood counts and the increase in the sleep size, which is associated with the disease in the mice.

"We have now shown pretty conclusively that we can use this approach to treat mouse models of human Myeloproliferative neoplasms, results which provide a much more tangible prospect of success in humans," said Dr Zeidler.

"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 - a development that may ultimately provide substantial clinical and health economic benefits," he added.

The research team hopes to conduct a full clinical trial early next year. The findings of the study are published in Haematologica, the journal of the European Hematology Association and the Ferrata Storti Foundation.

Methotrexate

For more than three decades, methotrexate has been used to treat inflammatory diseases including rheumatoid arthritis, psoriasis, and Crohn's disease.

The safety and effectiveness of methotrexate are well documented, and millions of patients regularly take the drug. However, the mechanism by which methotrexate acts in inflammatory diseases had not previously been understood.

Diseases such as rheumatoid arthritis and psoriasis feature inflammatory processes driven by JAK/STAT pathway activation. The effectiveness of methotrexate in inflammatory disease may be a consequence of its ability to suppress the JAK/STAT pathway activation.

Polycythemia Vera

Polycythemia Vera, is a bone marrow disease characterized by an overproduction of red blood cells. In patients with Polycythemia Vera, the numbers of white blood cells and platelets may also be higher than normal. The overproduction of red blood cells results in very thick blood, which can't flow through small blood vessels. As the blood is thick, it increases the risk of blood clots, stroke, and heart attack. Patients with Polycythemia Vera have symptoms like itching, headache, weight loss, fatigue and night sweats. More than 3,000 people in the UK are diagnosed with Polycythemia Vera every year.

Facts on Polycythemia Vera:

• Polycythemia Vera occurs more often in men than in women
• Most patients with Polycythemia Vera do not have a family history of the disease
• It is not diagnosed in people under age 40
• It is often linked to a gene defect called JAK2V617F
• Polycythemia Vera is not curable, but can usually be managed effectively

References:

1. Kavitha Chinnaiya, Michelle A Lawson, Sally Thomas, Marie-Therese Haider, Jenny Down, Andrew D Chantry, David Hughes, Antony Green, Jon R Sayers, John A Snowden, Martin P Zeidler. Low-dose methotrexate in myeloproliferative neoplasm models. Haematologica, 2017; haematol.2017.165738 DOI:10.3324/haematol.2017.165738
2. Polycythemia Vera FACTS - (https:www.lls.org/sites/default/file/file_assets/FS13_PolycythemiaVera_FactSheet_final5.1.15.pdf)

Source: Medindia

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