Wednesday, March 16, 2011

Benlysta Approved By FDA

If I had a nickel for every time that I wished that the scientific world knew more about autoimmune disease, I'd have.......well, a whole lot of nickels.

It appears that research into the treatment of autoimmune disease is finally reaping some rewards far more valuable than nickels.

The FDA has approved the first new drug for use in the treatment of systemic lupus in fifty years. It's name is Benlysta (belimumab) and was co-developed by Human Genome Sciences and GlaxoSmithKline.

Benlysta is a monoclonal antibody (MAb) and is classified as a biologic agent. A biologic agent uses portions of the body's natural defense mechanisms to treat a disease. In this instance, Benlysta targets B cells - specialized white blood cells active in the autoimmune process. It limits B lymphocyte production by binding to a B lymphocyte stimulator (BLyS).You can read more about the specifics of this very interesting but technical discussion here and here.

Belimumab is not a cure for SLE, and it provides only modest success in treatment: only 30% of patients enrolled in clinical trial saw benefits. However, it may be beneficial for patients who are dependent on long-term steroid medications in reducing the use of steroids and in doing so, reducing also their potentially damaging side effects.

In studying this particular type of treatment, researchers also gained new and valuable information about the development and mechanics of SLE; this summary found on WebMD:

One of the hallmarks of lupus is that patients make antibodies to their own DNA, called anti-nuclear antibodies, or ANAs. Blood tests for ANAs are sometimes helpful as an initial step in diagnosing lupus.
Researchers had long wondered how that happens since DNA was thought to be protected inside cells. Then, in 2004, a team of researchers discovered that neutrophils can die in an explosive way, shooting strings of cellular material studded with proteins and bits of nuclear DNA out like webs to entangle harmful bacteria, viruses, or fungi. These neutrophil extracellular traps, or NETs, get slung outside the cell.
“They’re called NETs because they really look like a net, like a spider web,” says study researcher Michel Gilliet, MD, a dermatologist at University Hospital Lausanne, in Switzerland. The cells, he says, “shoot them out.”
In healthy people, once these NETs enter the liquid space between cells, the bits of nuclear DNA degrade quickly and probably don’t cause any problems, but Gilliet and his team found that patients with lupus have antimicrobial proteins called LL37 and HNP that appear to protect these bits of DNA from being broken down by the body.
Together, these proteins and DNA can trigger another type of immune cell, a kind of chemical factory called a plasmacytoid dendritic cell, which pumps out proteins that stoke the immune response.
One of those proteins, called type 1 interferon, is often present in high amounts in patients that have lupus, which has largely been another mystery of the disease.
Type 1 interferon, it turns out, triggers neutrophils to release more NETs, setting up an apparently self-perpetuating disease process.
“What this suggests is that there is a vicious cycle between the production of interferon, the way the neurtrophils die and the increase in the production of auto-antibodies, so this is a very, very efficient pathogenic loop that amplifies itself,” says study researcher Virginia Pascual, MD, an instructor of medicine at Baylor Institute of Immunology Research in Dallas.
You can read more about these new findings in autoimmune research here.


Jenny P said...

Ok once I shake off that creepy feeling from reading about the NETs...ick... Your (fabulous) summary notes that this is an issue in people with high ANAs. Since, as we know, ANAs are also seen in other conditions (including my buddy SjS), does that by proxy mean other people with elevated ANAs are experiencing the same thing...and taking it one step further, that Benlysta could be beneficial for us as well? I mean, in theory?

Anonymous said...

That's a so ggod news, first that a new drug is available for lupus patient, and that doctor are searching ! It's an hope for a lot of people !!

Julia Oleinik said...

Hm. Great question, Jenny. I'm not sure. I believe that the ANA elevation in Sjogren's syndrome is the result of autoantibodies to very specific parts of DNA, and that in lupus, the autoantibodies attack other segments of DNA.

Good question - and good quest for me to find out more. I'll keep you posted.