New Drug Could Speed up Blood Cell Recovery after Chemotherapy
A drug that speeds up the regeneration of both mouse and human blood stem cells after radiation exposure could be used to successfully mitigate the side-effects of chemotherapy.
Although radiation chemotherapy can be an effective cancer treatment, as it preferentially targets cancer cells over normal body cells, it can cause long lasting side-effects in patients. Chemotherapy can suppress the activity of blood stem cells, which detrimentally affects immune system function.
Previous research has identified the protein tyrosine phosphate-sigma, known as PTP-sigma, as having regenerative effects in neurons. When PTP-sigma is activated in neurons the cell cannot regenerate, but without the action of PTP-sigma the cell can regenerate. Researchers identified that the PTP-sigma is present in blood stem cells and performs a similar function to help the cell recover from damage or injury. Mice who had deficiencies in the gene coding for PTP-sigma showed a faster rate of red blood cell regeneration after radiation exposure.
Researchers attempted to find a drug molecule that could bind to and block PTP-sigma. However, phosphate proteins are difficult to selectively target as they share similar active sites. As different phosphate proteins control a range of different functions, if the drug targets other phosphates in addition to PTP-sigma there is a high risk of side effects.
100 potential drug molecules were investigated for their effectiveness in selectively targeting PTP-sigma. Human blood stem cells were exposed to radiation in a lab dish and then treated with one of the targets molecules. The recovery rate of the cells was measured, finding that compound DJ009 was the most effective at enabling cell recovery.
The stem cells treated with DJ009 were implanted into mice with impaired immune systems. The regenerated cells were able to restore immune system function. New mice were then exposed to high doses of radiation, with some given DJ009 and others receiving no treatment. Nearly all the mice that received DJ009 survived, whilst more than half of those that did not, died within three weeks.
When the mice were exposed to radiation doses to represent chemotherapy treatment, the mice treated with DJ009 had restored normal blood cell counts within two weeks. The mice that were not treated with DJ009 displayed extremely low levels of white blood cells.
The researchers next aim to start human trials to determine if DJ009 could be developed into an effective recovery treatment post-chemotherapy.