Cancer drug may reduce kidney disease in lupus

[Guest guest]

Public release date: 8-Sep-2004

Contact: Conn

rconn@...

336-716-4587

Wake Forest University Baptist Medical Center

Cancer drug may reduce kidney disease in lupus

WINSTON-SALEM, N.C. ­ 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 online 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 M. Reilly, Ph.D., from

Virginia-land Regional College of Veterinary Medicine at Virginia Tech

in Blacksburg, Va., S. Gilkeson M.D., of the Medical University of

South Carolina in ton, 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.