February 22, 2021
In a recent study published in Arthritis & Rheumatology, LRA-funded researcher Dr. Xian Zhang found that a low dose of the chemotherapy drug topotecan reduced the inflammation and kidney damage of lupus nephritis. Topotecan was as effective as high doses of cyclophosphamide, another chemotherapy that’s currently used to treat severe lupus nephritis in people with SLE. The results suggest that topotecan may offer another treatment option for patients with lupus nephritis that causes fewer side effects than cyclophosphamide.
The chemotherapy drug cyclophosphamide is an U.S. Food and Drug Administration approved treatment for patients with severe lupus nephritis. However, it must be given in high doses, which means that some patients can experience major side effects like infertility and bladder damage. Many patients cannot continue taking cyclophosphamide due to these side effects and need additional treatment options.
Topotecan is another U.S. Food and Drug Administration approved chemotherapy drug that may help treat lupus nephritis. Topotecan acts by interfering with a molecule known as Fli-1 that is found inside of many immune cells, including B cells, which contribute to lupus nephritis. Fli-1 within B cells helps them produce proteins called antibodies to help the body fight microbes. But some antibodies cause the body to mistake normal human cells for microbes. This means that the immune system attacks and destroys healthy cells that the body needs to function. People with lupus and lupus nephritis have extra B cells that attack human cells.
Dr. Zhang’s research group previously discovered that topotecan could reduce inflammation in cells from lupus patients. However, it was not tested in people or animals with lupus nephritis. In this study, Dr. Zhang tested a low dose of topotecan in mice with lupus nephritis and compared it to cyclophosphamide. After treating mice with a low dose, he found that topotecan greatly reduced kidney injury and inflammation and improved the overall survival of the mice as well as cyclophosphamide. Another chemotherapy drug, camptothecin, also effectively protected mice from kidney injury.
Dr. Zhang’s findings suggest that topotecan and camptothecin may be effective in treating lupus nephritis. He concluded that though more research is needed, both agents offer promising therapies for lupus nephritis with fewer side effects than cyclophosphamide.