Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


New compound holds promise for lupus and related diseases


A chemical cousin of anti-anxiety medications, such as Valium and Xanax, significantly reduces kidney inflammation in mice inbred to develop a disease resembling human systemic lupus erythematosus (SLE), researchers at the University of Michigan and the University of California-Berkeley have found.

Their research, described in the Oct. 16 issue of the Journal of Clinical Investigation, also reveals the novel mechanism by which the compound works, a discovery that could lead to safer and more effective new drugs for managing lupus and other autoimmune disorders.

"The best available therapies for lupus haven’t changed for many, many years," says U-M’s Gary D. Glick, Ph.D., one of the lead authors on the study. "It’s a disease where the mechanisms that normally prevent the immune system from attacking components of one’s own body are defective. Because we do not yet understand what triggers lupus, it has been very difficult to develop lupus-specific therapies."

In fact, the mainstays of treating lupus-related kidney inflammation---the major cause of illness and death in lupus patients---are drugs developed many years ago to kill cancer cells. When given to lupus patients, often in combination with immune-suppressing steroids, these cytotoxic agents kill immune cells. But because they lack specificity, they also kill healthy cells, resulting in serious side effects. What’s more, they simply are not effective in some patients.

"Our compound, on the other hand, goes in and kills the bad players but leaves the good players alone," says Glick, a charter faculty member of the U-M Life Sciences Institute, who is the Werner E. Bachmann Collegiate Professor of Chemistry, and a professor of biological chemistry in the U-M Medical School.

The compound, a 1,4-benzodiazepine (designated as Bz-423), sets off a chain of events that results in apoptosis, a natural cell-suicide process by which the body rids itself of cells it no longer needs. In autoimmune disorders such as lupus, something interferes with apoptosis, and immune system cells survive and run amok instead of dying on cue. The abnormally surviving immune system cells produce antibodies, which attack the body’s healthy cells and tissues. The result is harmful and sometimes fatal inflammation in various tissues and organs, particularly the kidneys.

According to the Centers for Disease Control and Prevention, lupus affects 1.4 million Americans, and more than 22,000 have died as a result of the disease over the past 20 years. Women of childbearing age are at greatest risk, and African Americans are more likely than Caucasians to develop the disease, says Anthony Opipari, M.D., Ph.D., assistant professor of obstetrics and gynecology and a lead author of the study.

In an attempt to find new drugs for treating lupus, Glick and his co-workers screened a collection of benzodiazepines to identify any that killed immune cells. They chose benzodiazepines because unlike most cytotoxic drugs, these compounds do not damage DNA or interfere with cell metabolism. "We suspected that any benzodiazepines that were capable of killing cells would possess unique modes of action and perhaps be better at targeting disease-causing cells," says Glick.

In a series of experiments using cultured B cells (immune cells that make antibodies), the researchers found that Bz-423 targets a protein inside the cells’ mitochondria. To test the effectiveness of Bz-423, Glick and his team then gave the compound to mice with lupus. At the end of the treatment period, 60% of untreated mice had lupus-related kidney disease, compared to 16% of treated mice. The treated mice showed none of the side effects caused by currently available lupus drugs.

"The results suggest that Bz-423, when administered appropriately, may have a significant therapeutic potential for lupus," says Glick. There is also evidence that Bz-423 may be useful in treating some types of cancer, as well as other autoimmune diseases, and the researchers are actively pursuing these possibilities, according to Opipari.

"This paper illustrates the wonderful opportunities there are for chemists, such as Drs. Glick and Ellman, who are willing to venture beyond the lab and apply their skills to significant problems in human health," says John M. Schwab, a program director at the National Institute of General Medical Sciences, which supported the research. "At the same time, it shows that clinicians and patients can benefit by including a chemical or molecular perspective in thinking about how to combat a complex, life-threatening disease."

Working with a compound that belongs to one of the most well-studied families of drugs---the benzodiazepines---is remarkably helpful in moving Bz-423 into clinical trials, because so much is already known about chemical and pharmacological properties of that group, Glick says. Although Bz-423 is structurally similar to anti-anxiety drugs such as Valium and Xanax, subtle structural differences give it some advantages. For example, Bz-423 does not cause drowsiness or lead to addiction, says Glick.

After completing additional research on Bz-423, Glick plans to apply to the Food and Drug Administration for permission to test the compound in humans. The University of Michigan has applied for several patents on the medical and pharmacological properties of the compound and its molecular target.

In addition to Glick and Opipari, authors of the paper include M.D.-Ph.D. students Neal B. Blatt, Jeffrey J. Bednarski, and Kathryn M. Johnson; Anthony Boitano, doctoral student in chemistry; Roscoe L. Warner, Ph.D., research investigator in pathology; Raymond L. Yung, M.D., Ph.D., assistant professor of internal medicine; Bruce C. Richardson, M.D., Ph.D., professor of internal medicine; Kent J. Johnson, M.D., professor of pathology; and Jonathan A. Ellman and Francesco Leonetti of the University of California-Berkeley. The research was funded by the National Institutes of Health and the U-M Multipurpose Arthritis Center.

Additional Contact:
Nancy Ross-Flanigan,, (734) 647-1853

Sally Pobojewski | EurekAlert!

More articles from Health and Medicine:

nachricht NIH scientists describe potential antibody treatment for multidrug-resistant K. pneumoniae
14.03.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht Researchers identify key step in viral replication
13.03.2018 | University of Pittsburgh Schools of the Health Sciences

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>