Ankylosing spondylitis (AS)
AS is an inflammatory arthritis and enthesitis involving the spine and peripheral joints. About 350,000 pople in the US ahve AS. Traditional therapies, including disease modifying antirheumatic drugs, nonsteroidal antiinflammoatry drugs and corticosteroids do not adequately control diase activity in most patients. Etanercept (TNF receptor) has been shwon to substantially reduce diase activity. (Davis, Arthritis & Rheumatism, 48(11), 2003, pp. 3230-3236).
Osteoarthritis
Osteoarthritis is a type of arthritis caused by the breakdown and eventual loss of cartilage of one or more joints. Among the 100 different types of arthritis it is the most common, affecting more than 20 million people in the US. Osteoarthritis occurs more frequently with increasing age. Before age 45, it occurs more frequently in males. After 55, it occurs more frequently in females. Osteoarthritis commonly affects the hands, feet, spine, and large weight bearing joints such as the hips and knees.
Mechanisms of the Disease: The disease mechanisms active in OA are unclear, but changes in the biochemical and biomechanical proeprties of joint carilage, changes in chondrocyte matrix synthesis, and finally, a gradual destruction of the matrix are characteristic of the disease process. The breakdown of articular cartilage in OA is mediated by various enzymes such as metalloproteinases, plasmin and cathepsin, which are in turn stimulated by various factors that can also act as inflammatory mediators.
–Interleukin-1 (IL-1) has been implicated as a mediator of anabolic and catabolic processes in the progression of osteoarthritis (OA). (Shamji, Arthritis & Rheumatism 56(1), 2007, pp. 3650-3661).
Symptoms: The diagnostic criteria for OA is based on the clinical presentation and decreased joint space. Since this depends on the actual destruction of joint cartilage, it will be made only late in the disease. Unfortunately, we lack routine methods to diagnose “preOA” or ongoing disease.
Treatments:
–Inhibitors of Aggrecanases: Administration of antibodies to specific sites where aggrecan is cleaved by aggrecanases has been proposed as a potential therapeutic method (US 5427954).
–Recombinant IL-1Ra: has been approved as treatment for RA. Signaling through the IL-1 receptor is modulated by IL-1 receptor antagonist (IL-1Ra) which competitively antagonizes the binding of IL-1.
(Shamji, Arthritis & Rheumatism 56(1), 2007, pp. 3650-3661) discloses development of IL-1Ra – elastin-like polypeptide (ELP) domain fusion proteins. ELPs are genetically engineered polypentapeptide biopolymers with structure homology to mammalian elastin. They are composed of pentapeptide repeats of Val-Pro-Gly-X-Gly and are soluble below their characteristic transition temperature and undergo an abrupt inverse temeprature phase transition to form micron-sized multiparticle aggregates upon heating. Introduction of the thermally responsive ELP tag on the end of IL-1Ra may yield high local doses and provides sustained release and lower systemic exposure for teht reatment of OA.
–Diet/Health Factors: Omega 3 supplements have been reported to be beneficial for arthritis. Loose weight because puts extra weight on your bones. Avoid saturated fats. Antioxidants such as vitamin C may help. Certain food groups like citrus foods, foods with selenium, seafood (crabs, Brazil nuts, weat germ (can sprinkle on anything), caratenes (bright orange, dark green vegetables). (hot chillis peppers, corn, squase). Bioflavonoids can also suppress enzymes that eroid cartelgeg (onions, deep colored grapes, berries and cherries). Spices may be beneficial too.
–NSAIDs (Non-steroidal anti-inflmaatory drugs):
—-diclofenac: Pennsaid
A number of patents such as US 8,252,838 and 8,546450 are directed to formulations and methods of using diclofenac. The patents are also listed in the FDA Approved Drug Proudcts With Therapeutic Equivlaence Evaluations (“Orange Book”).
Pennsaid 2% above is a nonsteroidal anti-finlammatory drug (NSAID) and the first FDA approved twice daily topical diclofenac sodium formulation for the treatment of pain of osteoarthritis fo the knees. The drug includes diclofenac sodium as the active ingredient, diemthyl sufloxide (DMSO) as a penetration enhancer, ethanol as a solvent which dissolves teh active ingredient for adsorption of the drug into the skin, and propylene glycol as a solvent/penetration enhancer, hydroxypropyl cellulose (HPC) as a thickening agent, glycerin as a humectant that hold water onto the skin and water as a solvent.
Juvenile Rheumatoid Arthritis (JRA):
JVA is the most common cause of disability in children. Its etiology is unkown, although circulating autoanitbodies are common. For example, studies have shown a highly significant association between early-onset pauciarticular JRA and circualting antibodies to the 43-kDa nuclear protein DEK (Adams, Arthritis Research & Therapy, 5(4), 2002. It is possible that the DEK antigen may be involved in the etiopathogenesis of JRA, perhaps by activation of CD8+ T cells (Ferero, Human Immunology 39, 443-450 (1998). However, one studies concludes that anti-DEK autoanitobdies are less specific for JRA than previously believed (Dong, Arthritis & Rheumatism, 43(1), 2000, pp. 85-93).
Psoriatic arthritis:
Psoriatic arthritis is a chronic inflammatory joint disorder that affects 5 to 8% of people with psoriasis. A significant percentage of these people develop progressive destructive disease. About 25% of psoriasis patients with joint inflammation develop symmetric joint inflammation resembling the joint inflammation manifestations of rheumatoid arthritis RA. Although the disease resembles RA, it does not produce the antibodies characteristic of RA. Psoriasis (a skin condition causing flare-ups of red, scaly rashes and thickened, pitted nails) may precede or follow the joint inflammation. The arthritis usually affects joints of the fingers and toes, although other joints, including the hips and spine, are often affected as well.