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Blood stem cells are found in the bone marrow and are responsible for the production of blood cells and immune cells. Chemotherapy and radiotherapy usually suppress the activity of these stem cells, requiring weeks and sometimes months to recover. University of California at Los Angeles (UCLA) researchers have synthesized a new drug that in laboratory animals speeds up the recovery time.
Previous research has identified a protein known as the tyrosine phosphatase-sigma receptor protein (PTP-sigma), mainly located in the nervous system and controlling the regeneration of neurons. When PTP-sigma in neurons is activated, it stops the regeneration of neurons, but without that, the nerves regenerate faster after an injury.
In 2014, John Chute, a member of the Center for Research on Regenerative Medicine and Stem Cell Eli and Edythe Broad at UCLA and Professor of Medicine and Radiation Oncology at the Division of Hematology / Oncology of the Faculty of Medicine David Geffen, with his research The team found that PTP-sigma is also present on blood stem cells. Its function is similar to its activity in neurons.
In their new study, Chute found that in mice with PTP-sigma gene deficiency, blood stem cells recovered more quickly after being damaged by radiation.
"We are very excited about the potential medical applications of these discoveries," Chute said.
PTP-sigma belongs to a family of proteins called tyrosine phosphatases. It is usually difficult to block this family of proteins with drugs, largely because most family proteins have similar activation sites, which means that any drug designed to affect them affects them all.
Chute collaborated with Michael Jung, the presidential chair in medicinal chemistry from UC and distinguished professor of chemistry and biochemistry at UCLA, to develop a drug capable of blocking PTP-sigma. Jung's group designed and synthesized more than 100 potential drugs that could work, and then Chute and his group tested them. They eventually reduced the number to one molecule, DJ009.
DJ009 caused the recovery of human blood stem cells in petri dishes. When they were then transplanted into mice whose immune system was deactivated, they then tested the drug, thus confirming the possibility that DJ009 works in humans.
"The power of this compound in animal models was very high," said Chute. "This has accelerated the recovery of blood stem cells, white blood cells and other components of the blood system necessary for survival. If found safe in humans, it could reduce infections and allow people to leave the hospital sooner. "
In their research, published in the journal newspaper Nature Communicationsalmost all mice receiving high doses of radiation and treated with DJ009 survived. But of the mice that received radiation and did not receive DJ009, more than half died within three weeks.
Another group of mice received chemotherapy doses similar to those used in men treated for cancer. Mice that did not also receive DJ009 had extremely low levels of white blood cells and neutrophils after two weeks. In the chemotherapy group receiving the drug, leukocyte levels returned to normal levels over the same period.
Researchers are currently optimizing the drug and similar drugs in order to move to clinical trials on humans.
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