Chemotherapy and radiation are two of the front-line weapons in treating cancer. They can be effective, even life-saving, but they can also be brutal, taking a toll on the body that lasts for months. Now a team at UCLA has developed a therapy that might enable the body to bounce back faster after chemo and radiation, and even make treatments like bone marrow transplants easier on patients.

New blood supply

First, a little background. Some cancer treatments use chemotherapy and radiation to kill the cancer, but they can also damage other cells, including those in the bone marrow responsible for making blood stem cells. Those cells eventually recover, but it can take weeks or months, and during that time the patient may feel fatigue and be more susceptible to infections and other problems.

In a CIRM-supported study, UCLA’s Dr. John Chute and his team developed a drug that speeds up the process of regenerating a new blood supply. The research is published in the journal Nature Communications.

They focused on a protein called PTP-sigma, found in blood stem cells, that acts as a kind of brake on their regeneration. Previous studies by Dr. Chute showed that, after radiation, mice with less PTP-sigma regenerated their blood stem cells faster than mice with normal levels of the protein.

PTP sigma

So they set out to identify something that could reduce PTP-sigma levels without affecting other cells. They first identified an organic compound with the charming name of 6545075 (Chembridge) that was reported to be effective against PTP-sigma. Then they searched a library of 80,000 different small molecules to find something similar to 6545075 (and this is why science takes so long).

From that group, they developed more than 100 different drug candidates to see which, if any, were effective against PTP-sigma. Finally, they found a promising candidate, called DJ009. In laboratory tests, DJ009 proved itself effective in blocking PTP-sigma in human blood stem cells.

They then tested DJ009 in mice that were given high doses of radiation. In a news release, Dr. Chute said the results were very encouraging:

“The potency of this compound in animal models was very high. It accelerated the recovery of blood stem cells, white blood cells and other components of the blood system necessary for survival. If found to be safe in humans, it could lessen infections and allow people to be discharged from the hospital earlier.”

Of the radiated mice, most that were given DJ009 survived. In comparison, those that didn’t get DJ009 died within three weeks.

They saw similar benefits in mice given chemotherapy. Mice with DJ009 saw their white blood cells – key components of the immune system – return to normal within two weeks. The untreated mice had dangerously low levels of those cells at the same point.

It’s encouraging work, and the team is already preparing for more research to validate their findings and hopefully take the next step toward testing this in people in clinical trials.