Recent Patents on Inflammation & Allergy Drug Discovery - Volume 2, Issue 3, 2008

Cumulative evidence suggests that the induction of the antioxidant/anti-inflammatory heme oxygenase (HO)-1 may play a protective role in allergic inflammation. HO-1 suppresses mast cell degranulation and cytokine synthesis. The up-regulation of the HO-1 pathway has a significant protective effect against airway inflammation, mucus hypersecretion, and hyper-responsiveness in a model of allergic asthma. Moreover, HO-1 inhibits T cell-dependent skin inflammation and differentiation and function of antigen-presenting cells. The precise underlying mechanisms for HO-1- based protection against allergic inflammation are not yet completely understood, but appear to involve the protective effects of HO-1 by-products, such as carbon monoxide (CO), biliverdin/bilirubin and free iron. Among the HO-1 byproducts, CO has been shown to mimic some protective actions of HO-1 in allergic inflammations. This article reviews the latest knowledge, recent patent and studies on the protective roles and mechanisms of HO-1/CO in inflammation and allergy.

Hereditary angioedema (HAE) is a rare familial disease characterized by recurrent self-limiting episodes of soft tissue swelling affecting different parts of the body. Acute HAE attacks range from benign, but disfiguring skin edema, to painful abdominal, and even life-threatening laryngeal attacks. The disease is caused by an aberrant C1 esterase inhibitor (C1-INH), which regulates complement, fibrinolytic, and contact pathways. Elevated serum level of bradykinin as a result of contact pathway activation is thought to be the major mediator of pain and edema formation in HAE. Current therapy of acute HAE attacks is limited and mainly offers symptom control. In the United States only fresh frozen plasma provides some reconstitution of C1-INH, but the efficacy and safety of this treatment is controversial. In some European countries two human derived C1-INH concentrates have been used successfully. Prophylactic therapy for patients with frequent HAE attacks is confined to attenuated androgens and in some countries anti-fibrinolytics and C1- INH are also used. To satisfy the unmet needs, investigation of one recombinant C1-INH, two drugs working on bradykinin pathway and two human derived C1-INH concentrates are underway. This review article also discusses some recent patents related to the filed.

Seasonal allergic rhinitis is characterized by seasonal rhinorrhea, nasal congestion/stuffiness, nasal and ocular pruritus, and paroxysmal sneezing. Symptomatic relief and improved quality of life can be achieved in the majority of patients by using pharmacotherapy appropriately. Mild cases can be managed with either an oral antihistamine or a nasal corticosteroid alone. More severe cases may require a nasal corticosteroid in combination with various agents. Immunotherapy is reserved for a selected group of patients. While all other interventions provide symptomatic relief, specific immunotherapy may have long-term effects. This review article also discuss recent patents related to the field.

Immediate-type allergies (type I) allergies to environmental allergens such as plant pollen, pet dander, food, honeybees' and wasps' venom affect around a third of the total population in developed countries. The diseases comprise a broad spectrum from rather mild diseases such as hay fever and skin reactions like urticaria to severe ones such as bronchial asthma, vomiting and diarrhea and finally anaphylactic shock. Type I allergies are caused by an errant immune response leading to the production of allergen-specific IgE. The usual algorithm for the diagnosis of type I allergies begins with obtaining a detailed patient history and continues with the confirmation by skin tests and/or in vitro measurement of IgE. Allergen biochips are a promising new technology for the in vitro measurement of specific IgE in type-I allergic patients. In contrast to conventional in vitro tools, they consist of multiple allergen components spotted onto a microarray. This allows to perform multiple analyses in a single measurement analysing patient-specific sensitisation patterns, the so called “component resolved diagnosis&rdquo. This review considers prospects and difficulties with this new technology and also reviews patents related to this field.

Omalizumab is a recombinant humanized monoclonal antibody. Use of omalizumab is reported to benefit significantly patients with inadequately controlled moderate-to-severe persistent allergic asthma that is not controlled with high-dose inhaled corticosteroids. However, recent studies suggest that omalizumab might play an important role in the treatment of other potentially IgE mediated disease processes including: urticaria and angioedema, atopic dermatitis, allergic rhinitis, nasal polyposis and severe ocular allergies. Furthermore, addition of omalizumab to immunotherapy protocols is reported to be highly advantageous. Although omalizumab is generally well tolerated, reports on potential anaphylactic reactions as well as an association with Churg-Strauss syndrome necessitate close monitoring. The data reviewed are discussed with the aim of underlining unmet needs and making recommendations for future studies on omalizumab use. This might better guide future clinical practice regarding omalizumab treatment. This review article also discussed some patent related to the field.

Leukotrienes, and especially cysteinyl leukotrienes have been shown to be involved in many processes that play a role in asthma pathophysiology: eosinophil recruitment, the most characteristic processes of asthma pathogenesis, increased mucosal secretion, which impairs the normal process of airway clearance and favors the development of mucus plugs, mucosal edema, caused by increased vascular permeability and bronchoconstriction, leading to smooth muscle hypertrophy. Latest progress in the understanding of chronic asthma pathology events underline the leukotriene synthesis pathway enzymes and different leukotriene receptors as potential targets of asthma treatment in children. Agents inhibiting the production of leukotrienes or agents antagonising their receptor's action, attract attention. Studies on molecular mechanisms of leukotrienes action have led to the development and patents of potential drugs including new 5- lipoxygenase inhibitors, 5-lipoxygenase-activating protein (FLAP) inhibitors, leukotriene B4 receptor antagonists, or nanoparticulate leukotriene receptor antagonist formulations.

The prevalence of food allergy and anaphylaxis in children is reported to be increasing in recent years. Evidence suggests that exposure to large doses of antigen might produce a suppression of the specific IgE response, so that the continuous contact with high doses of antigens favours the maintenance of tolerance In the same way loss of contact with allergen in children with specific IgE reactivity may favour a loss of tolerance with development of systemic reactions, while a progressive new contact with allergen may favour a specific tolerance induction. We hypothesize that widespread and uncontrolled use of elimination diets for atopic dermatitis may have played a role in the increase of allergy and anaphylaxis. Specific oral tolerance induction may be a possible therapeutic strategy. The article review food allergies caused by exclusion diet and also discuss recent patents related to the field.

Allergen specific immunotherapy, comprised of subcutanoues injections of increasing doses of allergen extracts, has been shown to be the only treatment able to influence the natural progression of allergic disease. Different forms of local immunotherapies, involving oral, sublingual and nasal routes of allergen adminstration, have also been considered in clinical practice. The inability of the protein to survive gastrointestinal physiological barriers is a generally encountered problem in oral administration of protein drugs. In order to overcome the problems of low allergen bioavailability and absorptivity, during oral immunotherapy, several stabilization strategies have been outlined in the recent years. This review focuses on interventions including: hexose monosaccharide, ethyl alcohol and water vehicles, oxygen-containing metal salt based preparations, particles with enteric coating, and poly (lactic-co-glycolic) acid microspheres. Regarding the enormous potential of oral responsiveness and/or oral tolerance, research that focuses on new and improved carriers or vehicles for safe allergen oral delivery has great potential in treating allergic diseases. This article also review some of the recent patent related to the field.

Allergic symptoms usually disturb daily activity of affected subjects. Anti-allergic drug is a specific group of drug designed for allergic symptoms. There are many anti-allergic drugs in use. In addition to oral anti-allergic drugs, there are also non oral anti-allergic drugs. Those forms of anti-allergic drugs are developed expecting for the rapid pharmacological reaction. In this article, the author will briefly review on the patents on non oral anti-allergic drug.

Allergic contact dermatitis (ACD) is a common skin disorder that has a high socio-economic impact with regard to the increasing number of industrial allergens that has potential harmful effect on the skin of manual workers. Its management relies on the use of topical anti-inflammatory drugs as well as the avoidance of the allergens inducing the disease. However, with regard to the ubiquitous character of many chemicals in the environment, treatment of the disease remains unsatisfactory. Understanding the molecular basis of the disease is of major importance in prospect of designing new therapeutic modalities. In this article, the various stages of the disease are reviewed as well as the recent advances in the understanding of the molecular basis of the mechanisms of the disease that would help to conceive new concepts for drug intervention. The article also reviews some of the recent patent relevant to the field.

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