Researchers in Germany and England have found the first direct evidence of the genetic function leading to lupus.
An enzyme that cleans up Dnase1 -- the waste produced by cells when they die -- may hold the key to unlocking a treatment for system lupus erythematosus, commonly referred to as lupus, according to research published in the most recent issue of Nature Genetics.
"The correlation between lack of Dnase1 as (a) clearance protein and SLE ... has perhaps helped to better establish the view that removal of cell debris is crucial for an organisms to prevent autoimmune disease, in particular SLE," said Dr. Tarik Möröy of the Institute for Cell Biology in Germany. He performed the research with Dr. Hans-Georg Mannhers of the Institute for Anatomy and Embryology.
Lupus is an autoimmune disease, attacking an individual's own tissues. An estimated 1.5 million Americans have lupus, which strikes women between 10 and 15 times more often than it does men.
With lupus, the body's own immune system attacks the DNA and proteins inside cells, causing inflammation that produces symptoms of arthritis, skin lesions, inflammation of blood vessels and the lining around the heart, and kidney failure.
The cause of lupus, and the development of an effective treatment, have eluded researchers for decades. Now, the disease is mainly treated with immunosuppressant and anti-inflammatory drugs, including steroids. A therapy using Dnase1 could treat patients before serious symptoms arise.
Möröy suggested that the Dnase1 therapy may be more useful in preventing the onset or early progression of SLE in high-risk candidates, rather than as a treatment for patients with full-blown lupus.
Researchers have tried in the past to treat lupus with drugs that contain Dnase1, but none have been successful so far, possibly because the studies weren't performed on a large enough group, Möröy said.
"There is the possibility that recombinant DNase1 might be effective," said Dr. Mark Walport, a professor at the Imperial College School of Medicine in London, who wrote a commentary to accompany the Nature Genetics paper.
Whatever treatment comes out of Dnase1 research, more work remains.
"I am afraid that a new therapy is not around the corner but has to await the outcome of further clinical trials," Möröy said.
Researchers believe one cause of lupus symptoms might be the inability of the body to clear DNA and protein debris from dead cells. The lingering cellular trash may provoke an immune response, they said.
Cellular trash is normally removed by special proteins, the most important of which is the Dnase1 enzyme, which has been proven in past research to have lower than normal levels of activity in lupus sufferers.
When researchers deactivated the Dnase1 enzyme in mice, they found that although they were healthy at birth, the mice developed lupus-like symptoms in six to eight months.
The Dnase1 discovery was a surprise to Möröy and his colleagues, who have been working with the genetic cause of the disease for only two years.
Before that, they were trying to find out whether Dnase1 was involved in a particular form of DNA degradation that is called DNA laddering and occurs in apoptosis, or programmed cell death.
"The finding that Dnase 1 deficiency leads to Lupus was completely unexpected to us, although with hindsight it now makes a lot of sense," Möröy said.
Möröy and his collegues will continue to decipher the genetic factors involved in lupus by studying the disease progression and severity in mice.
What are the chances that this study will translate to humans?
"One can never tell," Walport said, "but it is an interesting approach."
