Friday, October 30, 2020

Researchers Find New Drug That Could Halt Kidney Failure

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drug approved for the treatment of rheumatoid arthritis may also turn out to be the first targeted therapy for one of the most common forms of kidney disease, a condition that almost inevitably leads to kidney failure. A team led by researchers at Harvard-affiliated Massachusetts General Hospital (MGH) is reporting that treatment with abatacept (Orencia)appeared to halt the course of focal segmental glomerulosclerosis (FSGS) in five patients, preventing four from losing transplanted kidneys and achieving disease remission in the fifth. The report was issued online in the New England Journal of Medicine (NEJM).

“We identified abatacept as the first personalized, targeted treatment for kidney disease and specifically for FSGS, a devastating and largely untreatable disease” said Peter Mundel of the Division of Nephrology in the MGH Department of Medicine. “We also identified a biomarker that helps us discern which patients are most likely to benefit from therapy with abatacept.”

FSGS is characterized by the formation of scar tissue in the glomeruli, the kidney’s essential filtering units. Some forms of FSGS are inherited and some have no known cause, but the vast majority of cases develop in individuals with hypertension, obesity, or diabetes. Although the underlying mechanism is unclear, FSGS disrupts the function of podocytes, cells within the glomeruli that are crucial to kidney function. While treatment with steroids and some immunosuppressive drugs helps some patients, the drugs’ side effects make long-term use problematic.

Previous research by Mundel’s team found that the expression on podocytes of an immune molecule called B7-1 signaled the breakdown of the kidney’s filtering function, leading to protein leakage into the urine (proteinuria) and ultimately to kidney failure. Currently approved to treat rheumatoid arthritis and being studied for other conditions, abatacept inhibits the activity of B7-1, a molecule that is not expressed in healthy podocytes. After in vitro tests indicated that abatacept blocked the primary pathogenic effect of B7-1 expression in podocytes, the team tested treatment with the drug in five FSGS patients, four with recurrent disease affecting a transplanted kidney and one with treatment-resistant disease who was at high risk for kidney failure.

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