Friday, June 4, 2010

New Medications on the Autoimmune Horizon

Photo mine. 

On June 1st, I posted a blurb entitled Hope For New Treatment, which references a recent article from SELF magazine. The SELF article mentioned the use of three medications with potential for treatment of autoimmune disease: Estriol, Larazotide, and Benlysta. 

I thought it might be interesting to take a closer look at each of these medications. Here's what I found:

Estriol - trade name Trimesta - is a weak estrogen-producing molecule produced in the placenta of pregnant women. Without estriol, a pregnant woman's body would consider the fetus as "non-self" and produce antibodies to attack it. Or, in research terms, estriol offers immunologic privilege to the fetus. Interestingly, when estriol is being produced during the pregnancy of a woman with multiple sclerosis, not only does estriol protect the developing fetus, but the MS seems to move into a remissive state. Researchers theorized that administering estriol as a therapeutic drug could re-create this remission and decrease the development of the nervous system lesions produced in all MS patients. You can read more about estriol and it's potential for use in MS here. Trimesta's manufacturer is currently enrolling patients in phase II/III clinical trials. 

Larazotide Acetate has potential for reducing the effects of celiac disease, an autoimmune condition that attacks the intestines in response to the ingestion of wheat and gluten. People with celiac disease have been found to have elevated amounts of a specific protein - zonulin - in their gut. Zonulin, discovered by University of Maryland researcher Alessia Fasano, is believed to have the ability to "unlock" the barrier cells lining the intestines, lungs, and the brain to allow large molecules such as gluten to leave the intestines, causing disease. My explanation is does not do justice to this incredibly complex process, but you can read a more detailed explanation of celiac disease and zonulin in the article entitled Eating Away at You. Which brings us, finally, to the drug Larazotide, which blocks the zonulin receptor cells in the intestine and shows promise in the early stages of human trials. 

Benlysta (belimumbab) is a medication which is being developed for use in SLE, or lupus. Here is the manufacturer's description of it's actions:
BENLYSTA inhibits the biological activity of B-lymphocyte stimulator, or BLyS. BLyS is a naturally occurring protein discovered by HGS [7-8], which is required for the survival and development of B-lymphocyte cells into mature plasma B cells. Plasma B cells produce antibodies, the body’s first line of defense against infection. In lupus and certain other autoimmune diseases, elevated levels of BLyS are believed to contribute to the production of autoantibodies – antibodies that attack and destroy the body’s own healthy tissues. The results of prospective observational studies show a significant correlation of elevated levels of BLyS with SLE disease activity. BENLYSTA acts by: (1) specifically recognizing and binding to BLyS, (2) inhibiting BLyS’s stimulation of B-cell development, and (3) restoring the potential for autoantibody-producing B cells to undergo the normal process of apoptosis (programmed cell death). Preclinical and clinical studies show that BLyS antagonists such as BENLYSTA can reduce autoantibody levels in SLE.  
Benlysta showed enormous potential in the early stages of clinical trials, but at week 76, although showing a higher response rate than placebo, the difference between Benlysta treated patients and placebo patients was less than expected, implying that the effects of the drug may wane before 76 weeks of use. In a 4/21/10 press release from the Alliance for Lupus Research, this slightly disappointing data was delicately phrased as the "secondary endpoint did not reach statistical significance". 

Although these drugs are not available in the US at this point, they all show promise. And what's even more important - their development is proof of ongoing, significant research in the understanding and treatment of autoimmune disease. 

1 comment:

Anonymous said...

The celiac-disease med is really intrigating.
There is hope !!