Discovery of novel therapies for rheumatic diseases and associated pain requires suitable and relevant disease models: a comparison of monoarthritis and polyarthritis efficacy models.
Chronic pain associated with rheumatic diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA) affects millions of people every year. This pain subsequently affects almost every aspect of a person's life and has a substantial impact on economics such as health insurance, lost wages, reduced productivity and increased incidence of depression and suicide. These facts highlight the need fro relevant disease models to assess new therapies for both inflammation and pain associated with disease.
Biotechniques Application Forum Oct 08 View this article Arthritis Services
Discovery of novel therapies for asthma requires suitable and relevant disease models.
There is a major unmet need in the treatment of asthma, which is growing in incidence and prevalence in industrialized countries. The prevalance of asthma has doubled in the western world over the previous 20 years due to increased exposure to indoor allergans or workplace sensitizers, more pollution and overuse of beta-2 agonists. These facts highlight the need for novel therapies, which in turn requires suitable disease models.
Biotechniques Application Forum June 2008 View this article Asthma Services
Monoclonal Antibody Induced Arthritis: a shorter, more synchronized alternative to the classic CIA model.
Collagen-induced arthritis (CIA) in mice is widely used as an experimental model for rheumatoid arthritis. Initial symptoms of inflammation in the CIA model occur at approximately day 21-24 with the model requiring 6-8 weeks to complete. The induction of the disease is typically at 80% of the animals and varies from laboratory to laboratory and with the use of different collagen sources. The disease symptoms also appear at slightly different times, making therapeutic administration protocols more demanding technically. With the long study length, significant amounts of compounds are required to be prepared for use over the study duration. Furthermore, the lengthy study period also requires increased number of measurements and scoring periods, increasing the cost of the study further. These points illustrate some of the key issues in running a typical CIA model.
Biotechniques Application Forum Feb 2008 View this article Arthritis Service ArthritoMab™ Antibody
The Study of Lung Function: AHR Readouts in pre-clinical allergic asthma models.
In recent years, there has been much discussion as to whether methods of studying lung function in preclinical models of allergic lung inflammation are worthwhile. While some researchers maintain that the phsyiological differences in rodent lung function versus human lungs means that lung function studies are less meaningful, AHR (airway hyperresponsiveness) provides the most consistent diagnostic feature of asthma in response to chemicals such as Methacholine or Adenosine. For this reason, many researchers feel that in order for an asthma therapeutic to be efficacious, it must be shown to affect AHR.
Fall 2007 Target: Inflammation View this article View asthma services
Finding Breakthrough Therapies in the Treatment of Chronic Pain
Pain is associated with the threat or presence of tissue damage and protects the body by warning us to avoid potentially harmful situations. We sense pain through the activation of sensory neurons. The "first-order" sensory neuron resides in the dorsal root ganglion (DRG). Axons from the neurons within these ganglia innervate our skin, organs and bones. These fibers terminate either in specialized receptors that sense vibration, mechanical forces, heat etc., or they terminate as free nerve endings that are exposed to the chemical environment of the tissue.
Fall 2007 Target: Inflammation View this article View pain related services
Asthma: Measuring the Breadth of New Medicines
A range of preclical models is available for the research to attempt to establish the efficacy of a novel therapy for human asthma. The situation is further complicated by the fact that each of these models can have a wide variety of readouts. The importance of choosing a suitable model is highlighted by the fact that currently licensed therapies can have variable efficacies depending on the model and endpoints utilised. This article discusses the models that are currently available and highlights new advances in the field that can help researchers gain information on the mode-of-action of their therapy.
May 2007 EBR View this article View asthma services
Asthma as a Therapeutic Target
The prevalence of asthma, along with asthma-associated morbidity and mortality, continues to increase worldwide. It is estimated that between 5-12% of the world's population now suffer from the disease. Asthma therefore is an important target for the biopharmaceutical industry. Development of new therapeutics depends on suitable preclinical models. The goal of a preclinical asthma model is to reproduce the airway inflammation, mucus hypersecretion or airway hyper-responsiveness seen in human asthma.
Fall 2006: Target: Inflammation View this article View asthma services
Nociception, Neuropathic & Inflammatory Pain
Pain being one of the most uncomfortable sesations we experience, is a critical component of our body's defense system. It is a mechanism that allows us to remove ourselves from dangerous situations as we move away from noxious stimuli, prevents further damage as we escape stimuli that causes pain after an initial insult, and promotes the healing process as we take great care to protect an injured body part. Pain is divided into two main categories: acute and chronic pain.
Fall 2006 TARGET: Inflammation View this article View pain related services
Measure the Proteolytic Degradation of Aggrecan: Hallmark in the Pathology of Arthritis
Aggrecan is a large aggregating proteoglycan of articular cartilage making up 10% of the dry weight. It is responsible for hydrating cartilage giving it compressibility and resilience during joint loading, thereby playing a major role in the normal function of cartilage. Depletion of glycosaminoglycan bearing aggrecan fragments from articular cartilage is one of the earliest events in cartilage destruction.
Fall 2005 TARGET: Inflammation View this article Aggrecanase Assay Aggrecan Antibodies Aggrecan
Matrix Metalloproteinases
Matrix metalloproteinases (MMPs) comprise a family of secreted and membrane-bound endopeptides that hydrolyze extracellular matrix proteins (ECM). Based on their preferred substrates and structural features, MMPs can be divided into collagenases, gelatinases, stromelysins, matrilysins and membrane-type matrix metalloproteinases (MT-MMP). MMp mediated ECM degradation affects processes such as connective tissue remodeling, cell migration and cell micro-environment regulation. MMPs further affect cellular behavior by modulatin the activities of cytokines, growth factors cell surface receptors and other MMPs. In addtion to their normal function in developmental and repair processes, inappropriate MMP activity also participates in diseases processes including arthritis and cancer.
Spring 2005 TARGET: Inflammation View this article MMPs MMP antibodies MMP assay