UCSD, TargeGen team-up on blood disease treatment

By Terri Somers

Union-Tribune Staff Writer

9:01 a.m. April 7, 2008

A one-year scientific collaboration that included the University of California San Diego and the tiny local biotechnology company TargeGen has moved a treatment for a potentially fatal blood disease into human trials at record speed.

The experimental drug is also the first in clinical trials to be funded in part by California's taxpayer-supported stem cell institute. The work on the drug's development is documented in articles published Monday in the scientific journal Cancer Cell.

Scientists involved in the drug's development, as well as the head of the state stem cell institute, said the work is an example of how a collaboration of researchers from competing academic institutions and industry can speed the long and expensive process of drug discovery.

While it can take five to ten years to discover a potential drug and ready it for clinical trials, TargeGen and the scientists collaborated for about a year before the compound started human trials in February.

“The combination of research groups working together with a biotech company is just a superb story and I think it's one of the leading examples supporting the establishment of (the state stem cell institute,)” said Alan Trounson, a stem cell scientist and president of the institute.

“It demonstrates what can be done in this space and the impact of funding stem cell research. It happened in a time frame that I wouldn't have really believed,” Trounson said.

The team was led by the lab of Catriona Jamieson, a physician scientist at UCSD Moores Cancer Center, who used a $642,500 Seed Grant from the stem cell institute to fund part of her work. Also on the team was John Hood, director of research at TargeGen, as well as scientists from Stanford, Harvard and the Mayo Clinic.

The myeloproliferative diseases are caused by a genetic mutation that prompts the stem cells in bone marrow to produce too many blood cells, which can result in problems with blood clotting, heart attacks, stroke and in some cases leukemia.

Currently there is no drug to stop the progression of the disease. Attempts to treat it with cancer drugs have been widely unsuccessful because they target rapidly dividing cells and stem cells are not rapidly dividing, Jamieson said.

The speed with which this therapy was developed is directly attributable to this loose network of collaborators from the different institutes, Jamieson said.

In the past, researchers at different universities weren't quick to share ideas. That is changing because patients who are better educated and networked through the Internet are demanding better care, she said.

“They remind us that we need to work together like a soccer team, play our positions and make sure we go after things in a way that will be most effective for everyone. In that way, we all win,” she said.

Jamieson's work was also partially funded by the Mizrahi Family Foundation, a philanthropic organization representing one of her patients, Albert Mizrahi, who also allowed his stem cells to be used in the research.

There are already four people enrolled in the clinical trial that started in February. And others with the rare disease are lined up to participate as other clinical trial sites start enrolling patients, also as a result of networking on the Internet, Jamieson said.

The first trial is designed to specifically treat 40 people with a myeloproliferative disease called myelofibrosis, which means their bodies produce too many red blood cells or too many platelets, Hood said.

At some point, their bone marrow starts to burn out, which causes scarring, he said. When that happens, the prognosis can be grim.

The trial is expected to be completed during the first quarter of 2009.

As a physician scientist, Jamieson treats patients as well as conducting research. Prior to joining UCSD, she worked in the lab of Irv Weissman at Stanford, where she began looking into myeloproliferative disorders. She had treated people with the disease, all of whom had an enlarged spleen and a tendency to have blot clots.

A lot had been written about the disease and the suspected genetic mutation that was responsible for it, known as JAK2.

Jamieson wondered if the stem cells that create blood cells were the cause.

In the research documented in the Cancer Cell article, her team put human stem cells engineered to have the mutant gene into mice models to see if the over-expression of the single gene would cause the disease. It did.

To corroborate, she then injected stem cells of people with the disease into the mice, and achieved similar results.

Meanwhile, TargeGen was familiar with some of the same research on JAK2 mutation's that Jamieson had read, and had used its expertise to develop an pill that it thought would affect only that specific target in the cell. That therapy reversed the excessive production of red blood cells.

“We had an ability to see the potential and move on it quicker than larger companies have been able to,” said Hood.

Many companies would not invest millions into a potential therapy that has a relatively tiny market of 100,000 people in the United States, because it does not offer much potential for a return on the investment.

But TargeGen looked at myeloproliferative disease as akin to the chronic myelogenous leukemia for which Novartis developed Gleevec, its second best-selling drug, Hood said.

It is a rare disease, but this therapy may have the potential to have a profound effect on the patients who take it, he said.

While only 15,000 people a year in the U.S. are diagnosed with CML, it works so well people want to stay on it, he said. And there is now a global market, he said.

TargeGen wound up giving Jamieson funding so that she could do her own research on the company's so-called JAK2 inhibitor. The company was not to be involved in the research, or interpreting its results.

But it was there to offer guidance to Jamieson when she needed guidance on dosing the mice she used in her studies, or to consult with when she saw what she mistakenly thought might be toxicity.

Jamieson's study and another by Harvard University Schools of Medicine confirmed the therapeutic potential of the compound. Harvard's study was also published in Cancer Cell Monday.

“That effective dialogue allows us to be very quick in transitioning from the lab into the clinic,” Jamieson said. “We can't develop drugs appropriate for the clinic in an academic setting,” she said.

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