Developing the concept of adoptive cellular gene therapy of rheumatoid arthritis.
ABSTRACT Progressive destruction of articular cartilage and bone is the pivotal problem of rheumatoid arthritis (RA). Joint destruction is the cause of severe disability and determines the long-term outcome of disease. Conventional therapy does not control this destructive process sufficiently and the anti-rheumatic drugs available today can cause severe systemic adverse effects. Local application of chondroprotective and osteoprotective agents by means of gene therapy would be an attractive alternative to conventional therapy of RA and could provide long-term expression of the therapeutic agents and minimize systemic adverse effects. For this purpose, we have developed the concept of adoptive cellular gene therapy. This treatment strategy is based on using genetically engineered cells that home specifically to sites of autoimmune inflammation and thus allow local delivery of therapeutic gene products. Ex vivo transduction of these cells avoids systemic exposure of the host to the transgene-encoding vector and thus adds to the safety of this approach. In this article of the CIS Spring School in Autoimmune Diseases 2005 proceedings, we review our work on developing the strategy of adoptive cellular gene therapy and summarize recent advances in the evaluation of therapeutic effects and the identification of novel therapeutic targets.
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ABSTRACT: Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that is characterized by inflammation of synovial membrane and the release of inflammatory cytokines that ultimately results in joint destruction and disability. The therapeutic treatment plan for treating RA patient initiates with disease-modifying antirheumatic agents (DMARDs) and ends with the use of biological agents. Sometimes a combination of DMARDs and the biological agents are aggressively initiated. But this is not sufficient to retard the underlying progression of the disease and hence the disease-associated pain persists. The solution lies in the treatment of causative factors. Modern therapy aims at targeting newer target sites that can not only overcome the problem of pain and disability but also minimize the occurrence of adverse effects faced by the traditional therapeutic approach. Areas covered: This review covers the pathological background of the disease in brief, the traditional and newer biologicals, therapeutic targets and novel therapies for rheumatoid arthritis. Expert opinion: Better management of the disease can be achieved by focusing on the causes and the factors of the disease. Newer therapies and targeting sites discussed in this review focus on treating the disability at the cellular level without affecting body's immune response and minimizing the chances of infection and inflammation.Expert opinion on biological therapy 09/2012; · 3.22 Impact Factor
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ABSTRACT: The treatment of rheumatic diseases has been the focus of many clinical studies aiming to achieve the best combination of drugs for symptom reduction. Although improved understanding of the pathophysiology of rheumatic diseases has led to the identification of effective therapeutic strategies, its cure remains unknown. Biological agents are a breakthrough in the treatment of these diseases. They proved to be more effective than the other conventional therapies in refractory inflammatory rheumatic diseases. Among them, tumor necrosis factor inhibitors are widely used, namely Etanercept, Infliximab, or Adalimumab, alone or in combination with disease-modifying antirheumatic drugs. Nevertheless, severe adverse effects have been detected in patients with history of recurrent infections, including cardiac failure or malignancy. Currently, most of the available therapies for rheumatic diseases do not have sufficient tissue specificity. Consequently, high drug doses must be administrated systemically, leading to adverse side effects associated with its possible toxicity. Drug delivery systems, by its targeted nature, are excellent solutions to overcome this problem. In this review, we will describe the state-of-the-art in clinical studies on the treatment of rheumatic diseases, emphasizing the use of biological agents and target drug delivery systems. Some alternative novel strategies of regenerative medicine and its implications for rheumatic diseases will also be discussed.Tissue Engineering Part B Reviews 12/2009; 16(3):331-9. · 4.64 Impact Factor