MD Biosciences Blog

Cutting Edge Rheumatoid Arthritis Models

Posted by MD Biosciences on Jul 5, 2010 10:10:00 AM

Rheumatoid arthritis is a chronic and progressive inflammatory condition estimated to affect between 0.5% and 1% of the world’s population, with more women being affected than men. RA is a systemic disease manifesting mainly as a disabling destruction of the synovial joints of the hands and feet.  In addition to the disability and decreased quality of life caused by RA, patients are at increased risk of developing cardiovascular disease. Joint destruction is induced by dysregulated immune activation of both the innate and adaptive immune responses resulting in alterations in the synovium, cartilage and bone.  The normal joint has a thin synovial lining (intimal lining layer), 1-3 cells thick. Beneath this is a sub-lining layer of connective tissue scattered with immune cells, blood vessels and nerve cells.  Together these layers form the synovium, which produces the synovial fluid that serves to lubricate the joint. Disease initiation results in profound changes in the structure and composition of the synovium and synovial fluid; with the infiltration of inflammatory cells, synovial cell hyperplasia, increased angiogenesis, fibroblast proliferation and extracellular matrix production. This increase in synovial cell proliferation can result in the lining increasing up to five times its original size and can result in pannus formation. The culmination of these events is bone and cartilage erosion and loss of joint function.

Read More

Topics: Inflammation

Screening Assays | Targeting Fibroblast-like Synovioctyes

Posted by MD Biosciences on May 13, 2010 8:39:00 AM

Rheumatoid arthritis (RA) is a chronic autoimmune joint disease characterized by inflammation of the synovium and destruction of cartilage and bone. During synovial inflammation, inflammatory cells (macrophages, mast cells, dentritic cells and lymphocytes) are recruited while resident cells (fibroblast synoviocytes, chondrocytes, osteoclasts, and osteoblasts) are altered to support the inflammatory process.  Together, these events create a pathological tissue response.
 
The synovium consists of two layers, the sublining and intimal lining.  In RA, the sublining becomes infiltrated with mononuclear cells, B lymphocytes produce autoantibodies, blood vessels proliferate, lymphoid aggregates form and the intimal lining shows increased cellularity.  Macrophages in the synovium produce pro-inflammatory cytokines, chemokines and growth factors which in turn activate fibroblast-like synoviocytes (FLS) to produce their own array of mediators (e.g. proteolytic enzymes, chemokines and cytokines).  This produces a paracrine/autocrine network that leads to synovitis, the recruitment of new cells and the destruction of the extracellular matrix.  Fibroblast-like synoviocytes have emerged as key pro-inflammatory cells promoting the disease, largely due to their ability to produce massive amounts of degradative enzymes.
 
The availability of biological therapies has improved clinical outcomes by decreasing inflammation and joint destruction, however only about half of the patients exhibit substantial efficacy. Targeting FLS may further improve clinical outcomes without suppressing systemic immunity.  In vitro FLS assays can be used to evaluate effective therapies for arthritis. Using FLS obtained from normal, RA and OA patients, we can evaluate a compound's effect on the production of pro-inflammatory mediators in a preclinical in vitro model. 

Read More

Topics: Inflammation

Efficacy of anti-CD20 Therapy in Rhuematoid Arthritis

Posted by MD Biosciences on May 11, 2010 11:46:00 AM

We read an interesting article published this week in Journal of Immunology (v184 Bottaro & co.) on the efficacy of anti-CD20 therapy in RA. The article highlights the continuing uncertaintity over the mode of action of B-cell directed therapy in Rheumatoid Arthritis (RA) [review of the differing theories is presented in Clin Exp Immunol. 2009 Aug;157(2):191-7].

Read More

Topics: Inflammation

Determine Immunomodulatory Mechanism of Action for Compounds

Posted by MD Biosciences on May 5, 2010 9:42:00 AM

Determine immunomodulatory mechanism of action for compounds in indication discovery or respositioning of approved therapies.

Read More

Topics: Inflammation

MS Whitepaper: EAE Models | Evaluating Neuroprotective Treatment

Posted by MD Biosciences on Apr 20, 2010 9:12:00 AM

Cognitive impairment is common in multiple sclerosis (MS), occuring at all stages of disease. It is a main source of disability, social impairment and has a great impact on an individuals quality of life. In the clinic, factors that can affect MS-related cognitive impairment are disease course, fatigue, and affective disturbance.  While the neurochemical basis underlying motor and cognitive defects in patients with MS is unclear, it appears that a balance of tissue destruction, tissue repair and adaptive function reorganization are related to the degree of impairment.

Its most commonly believed that MS is an autoimmune disease in which the body's own immune system recognizes myelin proteins or myelin related proteins as foreign and marks them for destruction. In the body's periphery, major histocompatibility complex (MHC) Class II proteins expressed on the surface of antigen presenting cells (APC) mistakenly bind to these proteins. This causes a naive-T (Th0) to bind to the antige and undergo activation and differentiation. Adhesion molecules and matrix metalloproteinases (MMPs) help T-helper 1 (TH1) cells stick and penetrate the blood brain barrier (BBB) into the CNS, they engage antigen-MHC complexes and produce pro-inflammatory cytokines leading to damage in the CNS. 

Read More

Topics: Inflammation, Neuro/CNS