Research suggests targeted treatment strategies for lupus

Nov 11, 2007

New research provides clues about the causes of lupus symptoms and suggests specific new targeted treatment strategies, according to Nilamadham Mishra, M.D., from Wake Forest University Baptist Medical Center, in presentations this week at the American College of Rheumatology in Boston.

The studies looked at premature atherosclerosis in lupus patients as well as accelerated cell death that seems to be behind many of the disease’s symptoms. Lupus is an autoimmune disorder that can involve the joints, kidneys, heart, lungs, brain and blood. An estimated two million Americans have a form of lupus.

In one study, Mishra and colleagues looked at the potential mechanisms of premature atherosclerosis, which is one of the leading causes of death and disability in lupus patients. Even when they take drugs to lower their cholesterol, lupus patients still develop fatty buildups in their vessels, which can lead to heart attack and stroke.

Previous research by Mishra found that a new class of drugs being developed (histone deacetylase inhibitors) were effective at preventing atherosclerosis in mice prone to develop the disease. In the current study, Mishra and colleagues explored whether it is a specific histone deacetylase, number 9 (HDAC9), that causes the problem.

Histones are considered the master regulators in gene expression, and Mishra was the first to establish an association between abnormal histone codes and the complications of lupus in a mouse model of lupus.

In the current study, the researchers found that in atherosclerosis-prone mice, there is more HDAC9 than usual in the macrophages, which are cells within the artery walls that collect cholesterol and can lead to atherosclerosis. They found that these increased levels of HDAC9 increase inflammation in the arteries as well as the buildup of fatty tissue that may break off and cause a heart attack or stroke.

In mice macrophages that were genetically engineered to have no HDAC9, the researchers found the production of chemicals that promote inflammation were reduced and levels of cholesterol deposits were reduced compared to mice that produced normal levels of HDAC9.

“With the drug that inhibits HDAC9, we were able to decrease inflammation and remove cholesterol at the same time,” said Mishra. “This study suggests that specifically targeting HDAC9 without inhibiting other histone deacetylases will be helpful for atherosclerosis.”

In a separate study, scientists found a potential explanation for why cells in lupus patients die at an increased rate and accumulate in tissues. This accumulation of cells is believed to trigger the inflammation that causes symptoms.

“We have not previously understood why cells die at an increased rate,” said Mishra. “This new study suggests both a possible mechanism and treatment.”

The study examined microRNAs, chains of ribonucleic acid that are involved in cell proliferation and cell death. The goal was to explore the possibility that aberrant expression of microRNAs is responsible for the abnormal cell death in lupus patients.

The scientists analyzed blood samples from five patients with lupus and seven healthy people of the same ages and sex at two points during a three-month period. A particular microRNA, miR-16, was consistently increased in lupus patients compared to the healthy participants. The scientists suspect that having too much miR-16 inhibits genes that control cell death and may also inhibit natural cell progression – resulting in the accumulation in tissues.

“Understanding this connection may lead to targeted treatments to decrease levels of miR-16,” said Mishra.

Source: Wake Forest University

Explore further: New compounds protect nervous system from the structural damage of MS

add to favorites email to friend print save as pdf

Related Stories

Study shows troubling rise in use of animals in experiments

4 hours ago

Despite industry claims of reduced animal use as well as federal laws and policies aimed at reducing the use of animals, the number of animals used in leading U.S. laboratories increased a staggering 73 percent from 1997 ...

NY surveying banks on cyber security defenses

7 hours ago

(AP)—New York financial regulators are considering tougher cyber security requirements for banks to mandate more complex computer sign-ins and certifications from the contractors of their cyber defenses, the state's top ...

Life-saving train design is rarely used

7 hours ago

(AP)—Nearly a decade ago, the U.S. secretary of transportation stood at the site of a horrendous commuter train crash near downtown Los Angeles and called for the adoption of a new train car design that ...

Climate change may flatten famed surfing waves

8 hours ago

On a summer day in 1885, three Hawaiian princes surfed at the mouth of the San Lorenzo River on crudely constructed boards made from coastal redwoods, bringing the sport to the North American mainland.

Recommended for you

Mystery of the reverse-wired eyeball solved

Feb 27, 2015

From a practical standpoint, the wiring of the human eye - a product of our evolutionary baggage - doesn't make a lot of sense. In vertebrates, photoreceptors are located behind the neurons in the back of the eye - resulting ...

Neurons controlling appetite made from skin cells

Feb 27, 2015

Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, providing a patient-specific model for studying the neurophysiology of weight ...

Quality control for adult stem cell treatment

Feb 27, 2015

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.