A drug that is already being tested as an anticancer agent, especially in lymphoma, may also reduce the kidney disease that is a result of systemic lupus, according to a researcher at Wake Forest University Baptist Medical Center.
The drug, SAHA (suberoylanilide hydroxamic acid ), inhibited the onset of lupus-related kidney disease in mice with lupus, said Nilamadhab Mishra, M.D., an assistant professor of internal medicine - rheumatology, writing in the Sept. 15 issue of The Journal of Immunology, published on line today..
Systemic lupus affects an estimated 1.5 million Americans, mostly women, and about half have kidney damage. In systemic lupus, the normally protective immune system attacks the body’s own organs, damaging kidneys, heart, lungs, brain, blood or skin. Most people with lupus have achy or swollen joints, frequent fevers and prolonged or extreme fatigue.
Besides preventing kidney disease, SAHA decreased the size of the spleen in the mice and at the same time decreased the production of certain T-cells (a type of white blood cell) that are a key to the autoimmune disorder, when compared to mice with lupus that didn’t get the drug. It also decreased excess protein in the urine in the mice.
“Further studies are needed to delineate the most effective therapeutic regimen,” Mishra and seven colleagues reported in the article. They also need to determine “the precise mechanisms of the anti-inflammatory properties of SAHA in lupus.”
The mice in the study have a defective gene and spontaneously develop lupus, including lymph node swelling and increased spleen size, said Mishra.
The researchers reported that SAHA caused no adverse effects in the animals at the doses given.
Mishra said he hoped to start a phase I clinical trial of SAHA in lupus patients next year. Phase I studies are primarily concerned with assessing a drug's safety.
Mishra said it would be a double blind study, in which neither doctor nor patient will know whether they received SAHA or an inert placebo until the end of the study.
The compound is the second that Mishra and his colleagues have tested in mice that may lead to new treatment of systemic lupus. In February 2003 they reported in the Journal of Clinical Investigation that trichostatin A, or TSA, reduced excess protein in urine, inflammation of the kidneys and spleen weight.
Mishra’s colleagues in the study included Christopher M. Reilly, Ph.D., from Virginia-Maryland Regional College of Veterinary Medicine at Virginia Tech in Blacksburg, Va., Gary S. Gilkeson M.D., of the Medical University of South Carolina in Charleston, and scientists at the University of Miami Medical Center in Miami and Memorial Sloan-Kettering Cancer Center in New York. Reilly and Gilkerson were involved in the TSA research as well.
SAHA was developed at Memorial Sloan-Kettering and licensed to Aton Pharma Inc. in Tarrytown, N.Y., which helped pay for the study, along with a grant from the Alliance for Lupus Research. Aton Pharma Inc. recently became a wholly owned subsidiary of Merck & Co.