Studies show chance for existing drugs to treat Lupus

WINSTON-SALEM, N.C. New studies have shown that the anti-seizure medication Depakote and the cancer drug mithramycin show promise for treating the complications of lupus, according to Nilamadham Mishra, a rheumatologist at Wake Forest University Baptist Medical Center.

The study with Depakote was done to determine if the drug could prevent kidney and skin disease in mice with lupus. Mishra’s theory was that valproic acid helps reduce activation of B cells, which are white blood cells involved in the body’s immune response, including in the production of antibodies in lupus patients.

The study was designed to determine if Depakote reduces B cell activity by targeting histone deacetylases, which reduce the expression of genes. Half of a group of mice were treated for lupus with the drug, and half received a placebo, or inactive treatment. No mice in the Depakote treatment group developed skin disease, whereas all mice in the placebo group did. Also, 90 percent of treated mice had low levels of protein in the urine (high levels are a sign of kidney disease), compared to 20 percent of the non-treated group.

With the mithramycin study, the researchers theorize that the drug targets a specific transcription factor, Sp1, which is a protein that controls several genes, including one that causes end-stage renal disease and kidney fibrosis. They believe that reducing the activity of these genes may have a beneficial effect on patients with lupus.

Again, the test subjects were mice which were split into two groups, one which received the drug and the other receiving a placebo. At the end of the eight-week study, 90 percent of the mice in the non-treatment group had renal vasculitis, inflammation of the tiny blood vessels in the kidney that can lead to kidney failure, compared to 30 percent in the treatment group. In addition, 60 percent in the non-treatment group had high levels of protein in the urine (a sign of kidney disease), compared to 22 percent in the treatment group. Also, kidneys in the treatment group showed significantly decreased expression of the genes controlled by Sp1.

Mishra has said that the group hopes to test the treatment in patients with lupus. He said the drug could potentially help prevent kidney disease as well as treat it.