A new study conducted by researchers at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge has resulted in a breakthrough in the understanding of how autoimmune responses can be controlled.

In a normal immune system, the body develops immune cells to recognize foreign material, like bacteria. Once encountered, the immune cells respond to eliminate the foreign material. Any rogue immune cells that would attack the body itself are destroyed during development or are regulated by special cell. A key gene in these regulatory cells is called Foxp3. Those people that either lack the Foxp3 gene or have a mutated version of the gene have dysfunctional immune regulation which can result in autoimmune diseases.

As a part of the study, scientists created a genetically engineered form of Foxp3 that can change developing immune cells into regulatory cells that have the ability to suppress immune response. They then injected the engineered gene into animals that were missing the Foxp3 gene.

Said group leader Dr. Alexander Betz: “When administered to and activated in animal models of arthritis, the modified cells inhibit or even reverse the disease process.”

The scientists are now working on determining the molecular mechanisms involved in the functioning of the Foxp3 gene and applying that to human cells. In that research they need to ensure that the human form of the gene does not negatively impact the body’s immune system.

“If Foxp3 functions as a key developmental switch in human immune cells, there is potential for a new avenue of therapy development that could transform arthritis treatment” — Dr. Betz.

The study was published in the current issue of the journal PLoS Biology.

Originally posted 2008-11-14 12:00:58. Republished by Blog Post Promoter

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Baminercept was being investigated for use in RA patients who did not respond to treatment with conventional disease modifying anti-rheumatic drugs (DMARD), such as methotrexate. The primary endpoint was the measurement of patients who achieved a 50% improvement in the number of swollen, tender joints, as well as other clinical measures at week 14.

The secondary endpoints were defined as the proportion of patients with a 20% improvement and a 70% improvement in the number of swollen and tender joints as well as other quality of life measures.

The first Phase II study, known as 104RA202, included 380 patients with active rheumatoid arthritis did not have and adequate response to conventional DMARD therapy. This was a double-blind, placebo-controlled, multicenter trial designed to assess the efficacy of 5 different dosages of baminercept in combination with methotrexate over a 12 week period.

The second Phase II study, known as 104RA203, included about 120 patients with active RA that did not have an adequate response to tumor necrosis factor (TNF) inhibitors. This was also a randomized, double-blind, placebo-controlled, multicenter trial. It was designed to assess the efficacy of a 200 mg dose of baminercept over a 12 week period in combination with methotrexate.

Based on the results of these 2 trials, Biogen has decided to discontinue development of baminercept for treating rheumatoid arthritis. However, the company indicated that baminercept did have potential uses for treating other inflammatory diseases, such as Crohn’s disease and multiple sclerosis. As of now, there are no clinical trials scheduled for these conditions.

Originally posted 2008-10-23 11:36:26. Republished by Blog Post Promoter

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A - Right cartoid artery; B - Normal artery; C - Plaque buildup in artery

Researchers believe that inflammation, such as experienced in RA, may contribute to atherosclerosis, a build-up of plaque in arteries. They also found that drugs currently used to treat RA may also reduce RA patient’s risk of artery plaque build up and heart disease.

This study included 158 RA patients who were given an ultrasound exam of the carotid arteries to assess the thickness of the artery walls at the start of the study. Another ultrasound was given about three years later.

For this study, researchers gave 158 RA patients two ultrasounds three years apart to assess the thickness of their carotid artery walls. (Two common carotid arteries, one on each side of the neck, branch off into smaller internal and external arteries that deliver blood to the brain and face.) About two-thirds of the participants in the study were female, and the average age was 59 years at the beginning of the study.

The differences between the scans showed that 82 percent of the participants had some thickening in their common carotid artery, while 70 percent had thickening in the internal carotid artery. Those participants who were treated with anti-Tumor Necrosis Factor (TNF) medications, such as adalimumab (Humira) or infliximab (Remicade), had a 37 percent lower rate of thickening in their common carotid artery compared to people not on the medication.

The researchers also found that not all medications were helpful. People who took corticosteroids, such as prednisone, had an increased risk of carotid thickening, unless they were also taking a cholesterol-lowering medication known as a statin. Statin use seemed to counter the negative effect of the steroid, according to the study.

“One key finding of our study was that RA patients had to have both high levels of inflammation and higher numbers of traditional cardiovascular risk factors, like high blood pressure, diabetes, etc., in order for inflammation to be a risk factor for carotid plaque progression” – Dr. Jon T. Giles, lead investigator and assistant professor of medicine in the division of rheumatology at Johns Hopkins University in Baltimore

Giles also noted that high levels of inflammation in the body were associated with increased plaque deposits.

The study results were presented at the annual scientific meeting of the American College of Rheumatology in Atlanta in November.

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