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Feb 09, 2012
 |  BC Innovations  |  Targets & Mechanisms

HUS and them

Two groups have identified new strategies to treat or prevent hemolytic uremic syndrome, a potentially lethal complication of Escherichia coli infection. A team at the University of Toronto has suggested that the marketed CXC chemokine receptor 4 antagonist Mozobil plerixafor could be repurposed for the indication, whereas Carnegie Mellon University researchers have found that the natural metal ion manganese could neutralize the toxin that causes the condition.1,2

Hemolytic uremic syndrome (HUS) is caused by the release of Shiga toxins from pathogenic bacteria such as the O157:H7 strain of E. coli and triggers symptoms such as anemia, thrombocytopenia and acute renal injury.

There are no available tests to determine whether a patient with gastrointestinal

E. coli infection will develop HUS, and there are no therapeutics that actually neutralize the toxin. Current treatments are palliative and include dialysis, blood transfusions and corticosteroids. The mortality rate is 5%-7%, and many patients who do recover have long-term renal problems.3

Alexion Pharmaceuticals Inc.'s Soliris eculizumab is approved to treat atypical HUS, a rare genetic form of the disease that is not caused by Shiga toxins. The company is running a Phase II trial of the drug in Shiga toxin-driven HUS and declined to comment.

Now, Philip Marsden and colleagues have used genetic studies to identify the specific genes that are dysregulated by exposure to Shiga toxins. Marsden is professor of medicine and director of nephrology at the University of Toronto and chair in medical research at St. Michael's Hospital.

The team's genetic profiling studies showed that the toxin led to greater expression of genes encoding CXC chemokine receptor 4 (CXCR4; NPY3R), CXCR7 and chemokine CXC motif ligand 12 (CXCL12; SDF-1) than expression in untreated controls. These data suggested antagonizing the chemokine pathway could prevent the toxin's effects.

CXCR4 and...

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