Arthri­tis drug ig­nites hope for can­cer treat­ment

Muscat Daily - - FEATURES -

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 the 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. Re­searchers hope to con­duct a full clin­i­cal trial early in 2018.

An in sil­ico model of the po­ten­tial in­ter­ac­tion be­tween methotrex­ate and the JAK2 ki­nase do­main

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