Mode Of Action Of Plerixafor Unraveled

Scientists have discovered the exact mode of action by plerixafor, a drug commonly prescribed to stimulate immune responses in patients suffering from neutropenia.

AsianScientist (Nov. 19, 2013) – Scientists at the Agency for Science, Technology and Research’s (A*STAR) 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.

Neutropenia is a condition characterized by the lack of a type of white blood cells, also known as neutrophils, in one’s blood circulation. Patients with neutropenia who receive plerixafor become prone to oral, skin, genital infections and in worst cases, a fatal whole-body infection.

Previously, it was known that Plerixafor increases the concentration of these white blood cells in the blood by inhibiting a protein called CXCR4. This inhibition prevents neutrophils in the blood stream from returning to the bone marrow, which is the primary compartment where the white blood cells are stored and released. It is therefore commonly accepted that the efficacy of the drug 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. Results of the study were published in the Journal of Experimental Medicine (JEM).

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 use of the drug, which may help to reduce the risk of bacterial infections in neutropenic patients.

“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 neutropenia,” said team leader Dr. Ng Lai Guan from SIgN.

The article can be found at: Devi S et al. (2013) Neutrophil mobilization via plerixafor-mediated CXCR4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow.

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Source: A*STAR; Photo: Wikipedia Commons/CC.
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