Scientists bring to light mechanism of drug for infections

Scientists at A*STAR's Singapore Immunology Network (SIgN) have discovered the exact mode of action by plerixafor, a drug commonly prescribed to stimulate immune responses in patients suffering from neutropenia, which causes them to become prone to oral, skin, genital infections and in worst cases, a fatal whole-body infection . A better understanding of the drug's mechanism can improve its usage to more effectively reduce risk of infections in these patients.

Scientists at SIgN employed cutting-edge imaging techniques to analyze the effects of plerixafor on the white blood cell activity in the study which was published in the Journal of Experimental Medicine (JEM).

Neutropenia is a condition characterized by the lack of a type of , also known as neutrophils , in one's . Plerixafor increases the concentration of these white blood cells in the blood by inhibiting a protein called CXCR4. This inhibition prevents neutrophils in the from returning to the , which is the primary compartment where the white blood cells are stored and released. It is therefore commonly accepted that the efficacy of the arises only from the release of these white blood cells from the bone marrow.

However, scientists at SIgN found that the inhibition of CXCR4 by the drug actually plays a dual role – It increases the neutrophil count in the blood through their release from the lungs, while simultaneously promoting their retention in the blood stream. Discovery of this additional mode of action not only provides a deeper understanding on the drug's mechanism, it also contributes to a more effective utilization of the drug. The ground-breaking study creates the possibility of using a combined drug treatment to maximise release of white from both the bone marrow and the lungs. The approach may be more effective in reducing the risk of bacterial infections in neutropenic patients.

The team leader, Dr Ng Lai Guan from SIgN said, "We have identified the precise mechanisms of plerixafor treatment, which has important implications on its usage. We can understand through this study the effectiveness or limitations of the drug on certain patients and thereafter craft new clinical approaches to better treat them. Our study forms a conceptual framework to establish improved therapeutic strategies for ."

Acting Executive Director of SIgN, Associate Professor Laurent Rénia, said, "Basic research as such is important for us to fully understand how drugs work, so that we can put them to best use. This is a study which can potentially be translated into clinical applications to impact the health and lives of neutropenic patients."

More information: "Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow" by Sapna Devi et al . www.jem.org/cgi/doi/10.1084/jem.20130056

add to favorites email to friend print save as pdf

Related Stories

New drug approved for lack of certain white blood cells

Aug 30, 2012

(HealthDay)—The U.S. Food and Drug Administration has approved the drug tbo-filgrastim to treat certain cancer patients undergoing chemotherapy who have a condition called severe neutropenia, the FDA said in a news release.

Imbruvica approved for mantle cell lymphoma

Nov 13, 2013

(HealthDay)—Imbruvica (ibrutinib) has been approved by the U.S. Food and Drug Administration to treat mantle cell lymphoma (MCL), a rare but aggressive form of blood cancer.

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments