New Drug Targets Leukaemia Trio

by Erin Crighton

In 2005, a genetic mutation that causes three types of leukaemia was discovered. Now only 3 years later, a new drug has been developed that inhibits the gene mutation, and is already being moved into clinical trials.

The mutated gene, JAK2, is the cause for most cases of the three types of leukaemia; polycythemia vera, essential thrombocytosis, and primary myelofibrosis. These diseases cause the body to overproduce white and red blood cells, and platelets, which result many complications such as blood clotting. The JAK2 gene produces a specific enzyme (from the ‘tyrosine kinases’ enzyme family) that causes any extra blood cells to be transferred into the bone marrow. In the mutated version of this gene, the enzyme gets stuck in a certain position, which causes blood proliferation to run out of control because it is no longer regulated, therefore causing the overproduction of the white and red blood cells, and platelets.

The most promising drug, a compound called TG101348, specifically inhibits JAK2, but leaves the related enzymes unaffected. It is soluble in tissue which also allows it to be distributed throughout the body, and can simply be taken as a pill rather than an injection. Along with these benefits, this drug has a long half-life, meaning it will stay in the body for a sufficient amount of time, and doesn’t show non-specific toxicity.

The compound was first tested on mice, which proved the compound to be very affective, resulting in all mice induced with polycythemia vera that were given high doses of TG101348 survived. It actually reversed the symptoms, making the blood cell count return to normal, and proving the mice healthy. The results showed the drug eliminates clinical manifestation of the three types of leukaemia, without any toxicity.

Human clinical trials for the drug were approved based on the results of the studies performed on mice and more preclinical data, and began in March this year. Small doses will first be given to leukaemia patient to make sure no toxicities appear.

Research news article can be found at: http://www.hhmi.org/news/gilliland20080407.html