PubMed | Chiba University and Nihon Pharmaceutical Co.
Type: Journal Article | Journal: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics | Year: 2016
Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.
Ujiie H.,Hokkaido University |
Sasaoka T.,Hokkaido University |
Sasaoka T.,Nihon Pharmaceutical Co. |
Izumi K.,Hokkaido University |
And 6 more authors.
Journal of Immunology | Year: 2014
Complement activation and subsequent recruitment of inflammatory cells at the dermal/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoanti-bodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system. Copyright © 2014 by The American Association of Immunologists, Inc. All rights reserved.
Sasaoka T.,Nihon Pharmaceutical Co. |
Ito M.,Nihon Pharmaceutical Co. |
Yamashita J.,Nihon Pharmaceutical Co. |
Nakajima K.,Nihon Pharmaceutical Co. |
And 10 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2011
Inflammatory bowel disease (IBD) represents a group of chronic inflammatory diseases characterized by inflammation and relapsing gastrointestinal disorders. Recent studies have shown that Th17 cells, which are well known as key mediators of chronic inflammation, have a pivotal role in onset and development of IBD in humans and mice, alike. In recent years, it has been reported that IL-27, which is an IL-12-related heterodimeric cytokine consisting of EBI3 and p28 subunits, act directly on naive T cells to suppress the differentiation of Th17 cells. However, effects of exogenous IL-27 on the IBD are not well elucidated. To clarify the suppressive effect of IL-27 treatment on IBD, we applied the flexible linking method to EBI3 and p28 subunits and generated a single-chain human IL-27 (scIL-27). scIL-27 inhibited xenogenic mouse Th17 cell differentiation in vitro, indicating that scIL-27 also acts in mouse immune systems. In a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced mouse acute colitis model, subcutaneous scIL-27 treatment significantly improved the colon length, extent of necrosis, and ulceration and thickened epithelium and several pathological scores in a dose-dependent manner. scIL-27 clearly suppressed several inflammatory cytokines, including IL-17, in inflamed colon, except for anti-inflammatory cytokine IL-10. The mesenteric lymph node cells from scIL-27-treated mice also exhibited a reduced inflammatory response and, furthermore, a lower population of Th17 cells than those of PBS-treated mice. Finally, we showed the therapeutic efficacy of scIL-27 on TNBS-induced colitis even after active colitis was established. These results suggest new possible therapeutic approaches for IBD, including disorders such as Crohn's disease and ulcerative colitis.© 2011 the American Physiological Society.
Nihon Pharmaceutical Co. | Date: 2011-04-20
It is known that L-menthol controls smooth muscle contraction. In order to use L-menthol in practice as a digestive tract contraction inhibiting agent in digestive tract endoscopy, it is required to devise means of giving a formulation in which an L-menthol-containing formulation remains stable and transparent or little cloudy over a long time after the production and which shows little foaming at the administration. In the present invention, an antifoaming agent is further added to a formulation for inhibiting smooth muscle contraction or a peristaltic contraction in a digestive tract containing a L-menthol emulsion having an average particle size of less than 100nm. Thus, it is possible to obtain a formulation that remains stable over a long time, has a high light transmittance, and produces little foam when filled into a container and sprayed at a target area to inhibit contraction to facilitate observation of the area in endoscopic examination of the digestive tract etc.
Nihon Pharmaceutical Co. | Date: 2011-04-25
This is to provide a novel medicine and a food and a drink composition for treating aesthenopia excellent in improved effect of aesthenopia. The composition for the treatment of aesthenopia comprises chondroitin sulfate or a salt thereof.
Nihon Pharmaceutical Co. | Date: 2014-10-01
In order to improve the resection efficiency, operability, and safety of endoscopic mucosal resection operations, a method has conventionally been employed wherein a cushion agent such as physiological saline is injected into the layer below the area designated for resection, causing the lesion to lift and protrude (hereafter simply referred to as protrusion), after which the lesion is removed. It is difficult to accurately remove the intended area using conventional cushion agents because applying pressure to the protrusion tends to cause deformation thereof, the degree of protrusion is low, and the cushion agent diffuses immediately after injection into the peripheral tissue, thereby causing the protrusion to disappear. The present invention solves these problems by employing a polysaccharide having a pseudoplastic viscosity such as xantham gum, carrageenan, gellan gum, guar gum, locust bean gum, sacran, or the like as a cushion agent.
Nihon Pharmaceutical Co. | Date: 2010-06-28
The present invention provides an autoantibody production inhibitor which can specifically suppress the autoantibodies and which can effectively prevent or treat the autoimmune disease of autoantibody type. According to the present invention, there is provided an autoantibody production inhibitor comprising, as an effective ingredient, a fusion protein which consists of a protein (X) containing a site recognized by autoantibodies which are a cause of the autoimmune disease of autoantibody type and a protein (A) containing a fragment which exhibits the antibody-dependent cellular cytotoxicity of the antibody heavy chain constant region.
Nihon Pharmaceutical Co. | Date: 2014-02-19
The present invention provides a new fusion protein which can specifically suppress the autoantibodies, which can effectively prevent or treat the autoimmune disease of autoantibody type, and which can be expressed in an amount sufficient for industrial production. A fusion protein, characterized in that, a protein (X) containing a site recognized by autoantibodies which are a cause of the autoimmune disease of autoantibody type is connected to a protein (A) containing a fragment of the antibody heavy chain constant region which exhibits the antibody-dependent cellular cytotoxicity with a linker peptide (L) consisting of one or more amino acid (s), wherein the protein (X), the linker peptide (L) and the protein (A) are connected in this order by means of peptide bond from N terminal to C terminal.
Nihon Pharmaceutical Co. | Date: 2010-01-06
When acute hepatitis progresses to fulminant hepatitis, a large amount of hepatic cells are rapidly broken, and as a result, the prognosis is seriously worsened. Thus, it is important to prognose the progress of acute hepatitis into fulminant hepatitis at an early stage and quickly start an appropriate treatment therefor. Although the prognosis of progress into fulminant hepatitis becomes possible owing to recent advances in test methods and diagnostic techniques, there has been no appropriate prophylactic/therapeutic agent for fulminant hepatitis. The present invention provides a therapeutic agent for acute hepatitis or a prophylactic/therapeutic agent for fulminant hepatitis with little side effect. The problem of the invention was solved by using a composition containing apolipoprotein A-II.
Nihon Pharmaceutical Co. | Date: 2012-04-02
A new fusion protein which can specifically suppress the autoantibodies, which can effectively prevent or treat the autoimmune disease of autoantibody type, and which can be expressed in an amount sufficient for industrial production. A fusion protein, characterized in that, a protein (X) containing a site recognized by autoantibodies which are a cause of the autoimmune disease of autoantibody type is connected to a protein (A) containing a fragment of the antibody heavy chain constant region which exhibits the antibody-dependent cellular cytotoxicity with a linker peptide (L) consisting of one or more amino acid(s), wherein the protein (X), the linker peptide (L) and the protein (A) are connected in this order by means of peptide bond from N terminal to C terminal.