Leading the way to a cure


The Role of Sphingosine Kinase in SLE

Oates, James, MD

Medical University of South Carolina

Current treatments for lupus nephritis — lupus-related kidney disease — are often ineffective. They also have significant side effects, including infection and sterility. Thus, it is important to find new approaches for treating this often fatal disease. Researchers have discovered a new class of compounds that can prevent inflammation in mouse models of rheumatoid arthritis and inflammation of the colon. One such compound, ABC294640, inhibits the activity of a protein called sphingosine kinase, which converts the lipid sphingosine into the inflammation-causing sphingosine-1-phosphate.

With their ALR grant, Dr. Oates and his team plan to determine the ability of ABC294640 to prevent lupus nephritis in lupus-prone mice. Early studies using ABC294640 in these mice suggest that mice treated with this compound live longer and are less likely to develop signs of kidney disease. 

In a second study, the researchers will treat the mice with either ABC294640, traditional therapy (cyclophosphamide), or a combination of both to determine if the new compound works as well as traditional therapy in treating disease once it occurs, and if combining it with cyclophosphamide works better than the traditional therapy on its own. They will also conduct studies to investigate just how ABC294640 works to prevent disease.

Finally, the researchers will study people with lupus for signs that sphingosine kinase also contributes to lupus nephritis in humans. 

What this study means for people with lupus: The ultimate goal of these studies is to provide preclinical studies required before human trials can be started to evaluate ABC294640 as a treatment for lupus nephritis.

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