A drug originally developed to fight stomach ulcers is the key component of a stem cell therapy that could help patients who need bone marrow transplants after aggressive chemotherapy.

A clinical trial is underway at the Dana-Farber Cancer Institute in Boston to evaluate the new medical procedure, which could potentially help some terribly ill people recover from the collateral damage from cancer treatment.

"One of the treatments for leukemia is to give high doses of chemotherapy, which gets rid of the leukemia, but it also gets rid of the immune system,” said oncologist Leonard Zon of Children's Hospital in Boston. “And I need to replace the immune system, otherwise the patient will die.”

The usual way to treat a damaged immune system is a bone marrow transplant, but suitable donors are often hard to find. So, for the last five years, oncologists have been treating some patients with an infusion of blood from umbilical cords, which is easier to match.

“You rely on the stem cells in that cord blood unit to find their way to the bone marrow, and essentially take hold, engraft, and start generating red cells, white cells, and immune cells,” said Pratik Multani of Fate Therapeutics, which is sponsoring the trial.

But cord blood also has problems. Each dose contains enough stem cells to rebuild the immune system of a child, but not enough to heal an adult. Older patients require at least two units of blood, and that can cause some serious problems.

“Two cords go into a person and their immune systems are different, because they come from two different babies,” said Zon. “The immune systems start fighting each other, and then over a three month period one of them usually wins out. And nobody thinks that this fighting of the immune systems is a good thing.”

So Zon's team began hunting for chemicals that would encourage stem cells to multiply and then migrate into bone marrow, so that adult cancer patients would only need one dose of cord blood to recover.

They tested 2,500 different chemicals on zebrafish embryos and found that one of the chemicals , which had previously been tested for treating ulcers, made the zebrafish stem cells divide and collect in the bone formation areas.

“In the early 80’s the chemical had been given to patients who have high stomach acid,” said Zon. “There were five clinical trials with this chemical, and it actually worked and had a good safety profile.”

The drug never made it to market because more effective antacid treatments got there first.

In the first experiment, which started last month, the scientists thawed two units of cord blood, incubated one of them with the almost-forgotten chemical and gave a patient both the treated and untreated infusions. Eleven more patients will undergo a similar procedure.

Months later, they will check to see which set of stem cells stood their ground. If the treated cells win out, and the patients are healthy, there is a good chance that the chemical does give stem cells a boost.

Image: Fate Therapeutics.

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