Drug used to treat HIV might defuse deadly staph infections

We know that, Maraviroc (structure below, brand-named Selzentry, or Celsentri outside the U.S.) is an antiretroviral drug in the CCR5 receptor antagonist class used in the treatment of HIV infection. It is also classed as an entry inhibitor. It also appeared to reduce graft-versus-host disease in patients treated with allogeneic bone marrow transplantation for leukemia, in a phase 1/2 study.

Now  researchers from  NYU School of Medicine  suggests that an existing HIV drug called maraviroc could be a potential therapy for Staphylococcus aureus, a notorious and deadly pathogen linked to hundreds of thousands of hospitalizations each year.

The discovery arose from a serendipitous finding that was a part of a collaborative study between Dr. Torres, a bacteriologist, and immunologist Derya Unutmaz, MD, associate professor of microbiology and pathology and medicine, whose laboratories are adjacent to each other. 

They focused on a receptor called CCR5 that dots the surface of immune T cells, macrophages, and dendritic cells. Sixteen years ago, researchers at NYU School of Medicine discovered that CCR5 is the receptor HIV uses to gain entry into T cells in order to replicate, spread, and cause an infection that can progress into AIDS.

That same receptor has now been found to be critical to the ability of certain strains of Staph to specifically target and kill cells with CCR5, which orchestrate an immune response against the bacteria. The scientists discovered that one of the toxins the bacterium releases, called LukED, latches on to CCR5 and subsequently punches holes through the membrane of immune cells, causing them to rapidly die. The LukED toxin belongs to a family of proteins called leukotoxins, encoded and produced by Staph to fight off the immune system's defenses.

Ref : http://www.nature.com/nature/journal/vaop/ncurrent/full/nature11724.html

Drug used to treat HIV might defuse deadly staph infections

HIV drug may slow down metastatic breast cancer

The HIV drugs known as CCR5 antagonists (Maraviroc or Vicriviroc see below structures from left to right respectively) may also help prevent aggressive breast cancers from metastasizing, researchers from the Kimmel Cancer Center at Jefferson suggest in a preclinical study. 

Such drugs target the HIV receptor CCR5, which the virus uses to enter and infect host cells, and has historically only been associated with expression in inflammatory cells in the immune system. Researchers have now shown, however, that CCR5 is also expressed in breast cancer cells, and regulates the spread to other tissue.

What's more, blocking the receptor with the CCR5 antagonists Maraviroc and Vicriviroc, two drugs that slow down the spread of the HIV virus by targeting the CCR5 co-receptor of the chemokine CCL5, also prevents migration and spread of basal breast cancer cells, the researchers found.

"These results are dramatic," said Richard Pestell, M.D., Ph.D., FACP, Director of Jefferson's Kimmel Cancer Center and Chair of the Department of Cancer Biology at Thomas Jefferson University, and study senior author. "Our team showed that the CCR5/CCL5 axis plays a key role in invasiveness, and that a CCR5 antagonist can slow down the invasion of basal breast cancer cells."

"This suggests it may prove to be a viable adjuvant therapy to reduce the risk of metastasis in the basal breast cancer subtype," he added.

Basal tumors, which do not express the androgen or estrogen receptors or HER-2, are typically associated with metastasis and often do not respond to hormonal therapies. Current treatments include chemotherapy, radiation, and surgery, but all demonstrate poor outcomes, thus highlighting the urgent need for a specific targeted therapy for the subtype.

More : http://cancerres.aacrjournals.org/content/early/2012/05/25/0008-5472.CAN-11-3917

HIV drug may slow down metastatic breast cancer