Recent Patents on Inflammation & Allergy Drug Discovery - Volume 4, Issue 2, 2010

Regulatory T cells (Tregs) are one of the T cell subsets that have strong immune-suppressive activity. Contact hypersensitivity (CHS), clinically manifested as contact dermatitis, is one of the most frequently used mouse models to address cutaneous immune responses, and is composed of two phases: sensitization and elicitation. Recently, the role of Tregs in CHS has been investigated using newly generated genetically engineered mice. In this review, we will provide an overview of recent patents and the mechanism of Treg-mediated immunosuppression especially in terms of IL-10, CD39, CTLA-4, and RANKL, and discuss the role of Tregs in CHS during the sensitization and elicitation phases.

The natriuretic peptides (NPs) are a family of widely distributed, but evolutionarily conserved, polypeptide mediators that exert a range of effects throughout the body. There is growing realization that NP actions go far beyond volume and blood pressure homeostasis. Their pleiotropic effects include a significant role in regulating the immune system. Localization of NP receptors in various immune organs as well as in modulation of inflammation in vascular disease supports this hypothesis. Immune cells, including macrophages, dendritic cells, and T lymphocytes, express receptors for NPs. NPs are also involved in polarizing the immune response to allergens. NPs play an important role in shaping the early immune response to environmental antigens and appear to play a critical role in the interaction between cells of the innate and adaptive immune systems. The recent explosion of basic and clinical research has resulted in improved understanding of their molecular structure. This has facilitated development of chimeric forms of NPs as well as more convenient routes of administration. Thus, the NPs and their receptors could be exploited to develop therapeutics for the inflammatory and immune responses in wide range of diseases. Also discussed are several patents regarding NPs in the present review.

Inflammatory bowel disease (IBD) consists of Crohn's disease (CD) and ulcerative colitis (UC). It is thought to be caused by genetic, abnormal immune response of the intestinal immune system and dysfunction of intestinal mucosal barrier against enteric bacteria. Mutational genes can affect the development of IBDs via certain signaling pathways. The abnormal signaling pathways play an important role in the inflammatory process and can lead to dysregulation of the inflammatory response and are crucial in the pathogenesis of IBDs. The signaling pathways mainly include P38 MAPK, JNK MAPK, PI3K/Akt, NF-κB signaling pathways. Intestinal microorganisms play a key role in the initiation and maintenance of disease. Disorders of signaling pathways including TLR, NF-κB can act on the intestinal barrier, and cause uninhibitedly release of effector T cells which are the central cells mediating inflammation in CD. This review highlights relevant patents and a new insight of signaling pathways associated with IBDs will help to develop better therapeutic approaches.

Intranasal corticosteroids offer effective symptomatic treatment of allergic rhinitis in children and adults. When used in recommended doses and administration regimens side effect profiles are acceptable and the risk of serious systemic adverse reactions is small. In children, assessments with the sensitive measure of knemometry has found reassuring results. Rigorous comparisons of specific intranasal corticosteroids in clinical use are not available and we have no knowledge as to whether variations in pharmacokinetic properties or bioavailability may reflect significant clinical differences. When the evidence on pharmacokinetics, bioavailability, systemic activity, side effects and efficacy are taken together, however, the most recently launched compounds fluticasone propionate, mometasone furoate, fluticasone furoate and ciclesonide seem preferable to older products. The documented once-daily administration, the quick onset of action and the concurrent effect on eye symptoms of the new drugs support the suggestion. Evidence for intranasal corticosteroids in pre-school children has not been provided. In this paper, a brief review of recent patents for the treatment of allergic rhinitis is also presented.

Anaphylaxis is the most concerning manifestation of hypersensitivity. Recent, thorough investigations on the pathophysiology of anaphylaxis achieved important advances in its understanding, regarding in particular the emerging role of mediators such as platelet activating factor (PAF) and sphyngosine 1 phosphate (S1P) and the improved knowledge on the actors of the signaling cascade, from the contact between the specific allergen and the IgE fixed on the Fc-epsilon-RI receptor to the opening of calcium channels. These advances may provide new diagnostic and therapeutical tools. In particular, a role for PAF and S1P as laboratory markers of anaphylaxis is likely to be developed, and innovative preventive strategies able to induce a negative signaling are currently under evaluation. Also, using well known preventive treatments, such as allergen specific immunotherapy may offer new perspectives for the management of patients at risk of potentially fatal reaction to foods. In fact, controlled studies demonstrated that sublingual immunotherapy is able to significantly increase the tolerance to the causative foods, fulfilling the need and protecting the allergic subject from anaphylaxis caused by accidental ingestion of small food amounts. The article also presented some promising patents on anaphylaxis.

The prevalence of allergic diseases has increased dramatically in recent decades. Holding patens is one of the means to protect good anti-allergy products. However, little is known of anti-allergy patent situation in China. The paper summarized and analyzed anti-allergy patents issued in China from January 1988 to September 2008. A total of 789 antiallergy patents have been granted in China during the 20 years. China, European countries, USA, Japan and other countries possesses 44%, 21%, 19%, 12% and 4% of all of these anti-allergy patents respectively. Interestingly, 88% antiallergy patents issued to Chinese are held by civilians, whereas vast majority of the patents issued to foreigners were held by pharmaceutical companies. All anti-allergy patents are focused on synthetic compounds, Traditional Chinese medicines (TCM), combinations of synthetic compounds and TCM (CST), biological products and medical apparatus. The anti-allergy patents in China mainly focus on well-known targets, such as histamine receptor and leukotrienes, which consist of 93% of patents for validated targets. Approximately 93% targeting diseases are bronchial asthma, allergic rhinitis and atopic dermatitis. Our analyzing results indicate that there are great opportunities for application of patents on development of novel anti-allergic compounds and modernization of TCM in China.

Plasmacytoid Dendritic Cells (pDCs) are important immune orchestrators. One of the most important features of pDCs is the high production of IFN type I that can promote the polarization of T cells towards a Th1 phenotype. Recent evidence has highlighted the relevance of pDCs in therapy for asthma, lung infections and cancer. However, it is to note that pDCs can also participate to suppressive networks via the recruitment of T regulatory cells. Further studies are needed to understand pDCs activity in the lung, not only to elucidate pathological mechanisms, but also to lead towards new therapeutic approaches for lung inflammatory-based diseases. This article outlines recent patents on plasmacytoid DCs.

Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid™, Lenalidomide) and CC-4047 (Actimid™, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-α (TNF-α), interleukins (IL) 1β, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of α glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies.

The majority of cancer patients will receive radiation therapy treatment at some stage during their malignancy. An acute skin reaction represents a common post radiation side effect with different grade of severity. In order to investigate the optimal methods to prevent and manage acute skin reactions related to radiation therapy we have conducted a systematic review on this topic. It seems that skin washing, including gentle washing with water alone with or without mild soap, should be permitted in patients receiving radiation therapy, to prevent acute skin reaction. In addition, a low dose (i.e., 1%) corticosteroid cream may be beneficial in the reduction of itching and irritation. We have concluded that there is insufficient evidence to support or refute specific topical or oral agents for the prevention or management of acute skin reaction. There is a need for further research to review treatments that have produced promising results in the reviewed research studies and to evaluate other commonly recommended topical treatments. The purpose of this patent and literature review is to advocate the current management of acute skin reaction.

Inflammatory bowel disease (IBD) including Ulcerative colitis (UC) and Crohn's disease (CD) is a major cause of gastrointestinal pathology in children and adolescents. Intestinal hyper-permeability plays a critical role in the etiology of pediatric CD by affecting the penetration of pathogens, toxic compounds and macromolecules; it also plays a central role in pharmaceutical product development. The mechanisms of barrier function and defects in permeability have great potential for guiding the development of novel drugs for treatment of IBD. Intestinal permeability is typically measured with the mannitol and lactulose tests in vivo; the results are expressed as the permeability index. The sensitivity and specificity of these tests are superior to other currently used surrogate markers in current CD clinical trials. However, the measurement of intestinal permeability has not been listed as a clinical endpoint. Somatropin (Growth Hormone) and Infliximab (anti-TNFα) have been used to treat pediatric CD. These agents significantly improve the inflammation in the GI tract and the imbalance of electrolytes in animals with colitis and CD patients by decreasing intestinal hyperpermeability. Herein, we discuss the feasibility of using intestinal permeability as an endpoint in the clinical trials of CD by current investigations and relevant patents.

Full text available