Recent Patents on Inflammation & Allergy Drug Discovery

ISSN: 1872-213X

Recent Patents on Inflammation & Allergy Drug Discovery

Volume 2, Number 2, June 2008

Contents


The IL-17 Family of Cytokines - Applications in Respiratory Medicine and Allergology Pp. 82-91
Martti Laan and Anders Linden
[Abstract]


New Strategies for Allergen Immunotherapy Pp. 92-101
Jerónimo Carnés and Douglas S. Robinson
[Abstract]


Patenting on New Topical Anti-Inflammatory Drug Pp. 102-104
Viroj Wiwanitkit
[Abstract]


Recent Developments in Phototherapy: Treatment Methods and Devices Pp. 105-108
Akimichi Morita, Mark Weiss and Akira Maeda
[Abstract]


Dihydropyridine Receptor Blockade in the Treatment of Asthma Pp. 109-116
Lucette Pelletier and Jean-Charles Guéry
[Abstract]


The Role of Bacterial DNA in Inflammatory and Allergic Disease Pp.117-122
Guo-Min Deng
[Abstract]


Placebos Used in Clinical Trials for Chinese Herbal Medicine Pp. 123-127
Guan D. Qi, Ding A. We, Leung P. Chung and Cheng K. Fai
[Abstract]


Recent Knowledge and New Pharmaceutical Products in Potential Alleviation of Endometriosis Pp. 128-138
Simon Vassiliadis and Irene Athanassakis
[Abstract]


Psychosocial Stress, Emotions and Cytokine-Related Disorders Pp. 139-148
Arnaud Aubert
[Abstract]


Influence of Prebiotics on the Human Immune System (GALT) Pp. 149-153
Pawel Bodera
[Abstract]


Patent Selections Pp. 154




Abstracts


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The IL-17 Family of Cytokines - Applications in Respiratory Medicine and Allergology
Martti Laan and Anders Linden

The excessive accumulation of granulocytes is believed to constitute an important factor in inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease (COPD). Notably, T helper (Th) cells are known to produce cytokines that are involved in the mobilization of eosinophils and neutrophils. Currently, it is believed that a third population of Th cells, the recently described Th17 population, accounts for the production of several members of the interleukin (IL)-17 family of cytokines. The members of this cytokine family have proven abilities to recruit and activate neutrophils and eosiniphils. This review summarizes the evidence that these cytokines constitute key mediators of the Th-controlled granulocyte influx in airway disease and points out molecular target candidates for therapy as well as related patents.


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New Strategies for Allergen Immunotherapy
Jerónimo Carnés and Douglas S. Robinson

Specific allergen immunotherapy, consisting in the administration of increasing amounts of offending allergens into sensitive patients was first used nearly one hundred years ago and remains in use worldwide for treatment of allergic rhinitis and asthma. It has been recognised as the only effective treatment for type I allergic diseases when the appropriate quantities of allergens are used. The immunological mechanisms by which specific immunotherapy is effective include the modulation of T cells and the response of B-cells and is accompanied by significant decreases of specific IgE and increases in allergen specific IgG antibodies, mainly IgG4. While specific allergen injection immunotherapy is highly effective and the most common way of administration other routes such as oral or intranasal ways have been considered as and alternative to subcutaneous injections.

During the last century, allergenic vaccines have been prepared using individual allergens adsorbed to different adjuvant substances. These vaccines have demonstrated efficacy and good results in different clinical trials. However, many novel approaches to allergen immunotherapy have been developed in the last years in order to increase the safety and efficacy of allergenic vaccines. In that way, different and modern vaccines have been prepared including more purified products such as depigmented allergen extracts; allergoids, consisting on big molecules of thousands of kDa, which contain all the individual allergens and show a significant decrease in severe adverse reactions; peptides or small aminoacid sequences; recombinant allergens; hypoallergenic vaccines where the IgE binding sites have been modified; or allergen-CpG fusion molecules. New presentations are under study and new treatments will be developed in the near future with the objective that the prevention of allergic disease may become a reality. The review article also discuss recent patent related to the field.


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Patenting on New Topical Anti-Inflammatory Drug
Viroj Wiwanitkit

Inflammation is a group of important pathological disorders in medicine. The main classical hallmarks for inflammation are pain, swelling and heat. Basically, there are two main groups of anti-inflammation drug, the steroid anti-inflammation drug and non steroid anti-inflammation drug, which is widely called NSAIDS. At present, there are many new anti-inflammatory drugs. Those new anti-inflammatory drugs are developed expecting for the better pharmacological reaction. In this article, the author will briefly review on the patents on new topical anti-inflammatory drug.


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Recent Developments in Phototherapy: Treatment Methods and Devices
Akimichi Morita, Mark Weiss and Akira Maeda

We review recently patented methods and devices that allow for more effectively targeted phototherapy with fewer side effects. Among the new devices and methods reviewed here are narrow-band UVB (311- 313 nm) with a flat-type light source and the new xenon chloride excimer light (308 nm), both of which allow for targeted spot irradiation, limiting the unnecessary exposure of healthy skin to UV light. Some new devices are designed to selectively irradiate targeted nasal and oral mucosal tissue and to deliver controlled doses of UV light. Devices that provide targeted phototherapy attenuate treatment-induced increases in skin temperature, thereby reducing tissue damage and increasing skin tolerance to high UV doses. Other recently patented methods include the use of irradiation efficacy enhancers, such as topical formulations of provitamin D and its analogs, followed by irradiation with UV and/or blue light. Combined phototherapy and electrotherapy therapy can also be used to treat selected skin areas. These new methods and devices are aimed at improving the safety and efficacy of phototherapy, especially targeted phototherapy.


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Dihydropyridine Receptor Blockade in the Treatment of Asthma
Lucette Pelletier and Jean-Charles Guéry

Asthma is a chronic airway disease resulting from inappropriate Th2-cell biased activation. Interleukin (IL)-4, IL-5 and IL-13 produced by Th2 cells contribute to the inflammatory process. Attempts for inhibiting interleukin-4 or IL-5 gave disappointing results. The simultaneous inhibition of several Th2-cytokines could be a more promising issue. Several arguments support the concept that Th2-cells express selective markers that could be targeted in asthma. Our group showed that Th2-cells selectively up-regulated dihydropyridine-sensitive Ca²⁺ (DHP-Ca) channels essential for Ca²⁺ signaling and type-2 cytokine production. Indeed, DHP-Ca antagonist effectively prevented or even reverted airway inflammation, airway remodeling and airway hyperresponsiveness in experimental models of asthma. Although it remains to be formally demonstrated that human lung infiltrating T-lymphocytes in asthmatic patients express DHP- Ca²⁺ channels, we hypothesize that targeting DHP-Ca channels in T-lymphocytes could represent an efficient strategy in the treatment of asthma.This review article also discussed patents relevant to the field.


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The Role of Bacterial DNA in Inflammatory and Allergic Disease
Guo-Min Deng

Bacterial infections can be localized to joints and brain causing septic arthritis and meningitis. Despite early and adequate antibiotic treatment, bacterial meningitis and arthritis remain an infection with a high mortality rate and severe sequelae. Bacterial DNA has recently been shown to exert immunostimulatory effects on leukocytes. We speculate that bacterial DNA may be involved in the process of bacterial arthritis and meningitis. We found that bacterial DNA and oligonucleotides containing unmethylated CpG motifs induce arthritis and meningitis by intraarticular or intracisternal inoculation. Arthritis and meningitis induced by bacterial DNA were characterized by an influx of monocytic, Mac-1+ cells and by a lack of T cells. Macrophages and their products such as tumor necrosis factor (TNF) alpha are essential for development of arthritis and meningitis triggered by bacterial DNA containing CpG motifs. In contrast, neutrophils, NK cells, and T/B cells were not important in arthritis and meningitis triggered by bacterial DNA. CpG ODN is also found to reverse Th-2 dominant allergic diseases. This review discusses that the role and mechanism of bacterial DNA in inflammatory diseases and allergic disease. In this review patented strategies are also discussed.


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Placebos Used in Clinical Trials for Chinese Herbal Medicine
Guan D. Qi, Ding A. We, Leung P. Chung and Cheng K. Fai

One of the important components in randomized Controlled Trial (RCT) is blinding. The gold standard of clinical trials is to achieve a double blind design. However, only a small number of randomized controlled trials in traditional Chinese medicine have been reported, most of them are of poor quality in methodology including placebo preparation and verification. The purpose of the article is to review the validity of placebo used in blinded clinical trials for Chinese herbal medicine (CHM) in recent years and related patents. We searched the Wanfang Database (total of 827 Chinese journals of medicine and/or pharmacy, from 1999 to 2005) and 598 full-length articles related to placebo clinical trials were found. 77 placebo blinded clinical trials for Chinese medicine were extracted by manual search from the 598 articles. After reviewing the 77 full-length articles, we found that nearly half of the clinical trials did not pay attention to the physical quality of the testing drug and placebo and whether they were of comparable physical quality. The rest provided very limited placebo information so that blinding assurance could not be assumed. Only 2 articles (2.6%) specifically validated the comparability between the testing drug and the placebo. Researchers in Chinese medicine commonly ignored the quality of the placebo in comparison to the test drug. This may be causing bias in the clinical trials. Quality specifications and evaluation of the placebo should deserve special attention to reduce bias in randomized controlled trials in TCM study.


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Recent Knowledge and New Pharmaceutical Products in Potential Alleviation of Endometriosis
Simon Vassiliadis and Irene Athanassakis

Endometriosis is so far considered as an incurable inflammatory disease. The ectopical implants of endometrial cells proliferate, increase in size and thereafter bleed following the menstrual cycle. The accumulated blood aggravates the situation by developing into cysts which, depending on the place, size and number, in most cases increase pain. Infertility in endometriosis is related either to mechanical distortion of the reproductive truck or to various endometriosis-induced factors including hormones, cytokines and chemokines. Except from the anti-inflammatory treatments and gonadotropin-releasing hormone agonists that have been used for a long time to relief from pain, new treatments are targeted against either hormonal-mediated cell growth via inhibition of the metabolic pathway of estrogens and androgens or vascularization or even implantation of the endometrial engraftment. Thus, the role of selective estrogen, androgen or progesterone receptor modulators, aromatase inhibitors, vascular endothelial growth factor receptor and extracellular matrix modulators is reviewed. This article also reviewed recent patents related to the field.


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Psychosocial Stress, Emotions and Cytokine-Related Disorders
Arnaud Aubert

It is quite clear from our daily experiences that psychosocial stress and emotional factors affects immunity and health. Moreover, from the first pioneer studies in the emerging field of study concerning the relations between emotions and immunity, stress has been commonly associated with immune-suppression. However, several evidence reveal a more complex relationship between emotions and immunity, thus offering new insights for the study of the impact of emotional factors in the onset, development or severity of many disorders, including autoimmune diseases. The present review summarizes background data concerning the crosstalk between brain and immune system and emphasizes the role of cytokines (in addition to the extensive influence of cathecolamines and glucocorticoid hormones) as key-molecules and discusses related patents.


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Influence of Prebiotics on the Human Immune System (GALT)
Pawel Bodera

Prebiotics have great potential to improve human health in specific intestinal disorders. The knowledge about the influence of prebiotics on the gut-associated lymphoid tissues (GALT) for the improvement of human health is still growing. This paper reviews the latest evidence for the immunity-enhancing effects of prebiotics. Prebiotics, include inulin, fructooligosaccharides, mannosoligosaccharides, and arabinogalactans, are a therapeutic nutritional preparation used for the gut function favoring growth of normal bacterial flora and impedes growth of pathogenic organisms. There is convincing preliminary data to suggest that the consumption of prebiotics can modulate immune parameters in GALT, secondary lymphoid tissues and peripheral circulation. There is increasing evidence that the newly described prebiotics and innovative means of administration can modulate various properties of the immune system, including those of the gut-associated lymphoid tissues (GALT). Authors of recently published patents showed new mechanisms for immuno-modulation, and the ultimate impact on immunological health of prebiotics.