Treatment reverses blood disorder in mice, study finds

By Julie Steenhuysen

CHICAGO (Reuters) - An experimental treatment in mice showed promise in reversing a rare blood disease that can cause leukemia, U.S. researchers said on Monday, offering a glimpse of how the drug may work as it begins testing in humans.

In experiments at Harvard Medical School in Boston and the University of California, San Diego, researchers found the compound blocked a genetic mutation that causes three kinds of leukemias.

The studies tested a compound supplied by privately held biotechnology company TargeGen in San Francisco, which has just begun early testing in humans.

It targets a genetic mutation in the JAK2 gene that causes most cases of the leukemias polycythemia vera, essential thrombocytosis and primary myelofibrosis, which affect up to 100,000 people in the United States.

The mutation in the JAK2 gene causes an overproduction of blood cells. The TargeGen compound TG101348 is designed to block the JAK2 mutation that causes this.

The idea is to set errant cells back on the right path, said Dr. Catriona Jamieson of the University of California, San Diego, whose paper appears in the journal Cancer Cell.

"By using how stem cells work and how they can go awry, we can redirect them using very targeted inhibitors that get these cells back on track," Jamieson said in a telephone interview.

Her experiments showed the compound reversed the disease in cell cultures. Her team also found the drug reversed disease in mice that had an engineered version of the mutant gene and those injected with stem cells from humans with the disorder polycythemia vera.

In a separate study in the same journal, Dr. Gary Gilliland and colleagues induced polycythemia in 168 mice. They gave high and low doses of the compound TG101348 daily for seven weeks to 112 mice. All the mice that got the higher dose survived, six in the placebo group died and one in the low dose group died.

"We saw that the compound alleviates and reverses the symptoms in mice," said researcher Gerlinde Wernig, who worked on the study.

"These are completely complimentary results," Jamieson said of the two studies, which helped lay the foundation for the human clinical trials which began last month.

Researchers at a half dozen prestigious medical centers will participate in the human studies, which will test a small dose of the drug in a few patients to see if it causes toxic side effects.

"Our goal is to get an efficacious drug into use for humans," said Gilliland, who is also a Howard Hughes Medical Institute researcher.