Therapy for Crohn disease

Sandborn, William J.

doi:10.1097/00001574-200007000-00005

Cited by 6 publications

(4 citation statements)

References 74 publications

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“…Current status of the diagnosis and the treatment of IBD are far from being ideal due to a significant lack of understanding of the pathophysiology. 1,2 However, the knowledge in genetic background is still growing. 3 Current knowledge indicates that the underlying mechanism leading to chronic inflammation in IBD is the inadequate immune response, which is caused by the dysbalance between inflammatory and anti-inflammatory agents and/or tolerance against gastrointestinal microflora.…”

Section: Introductionmentioning

confidence: 99%

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Salmonella-mediated gene therapy in experimental colitis in mice

Pálffy

Gardlík

Behuliak

et al. 2011

Exp Biol Med (Maywood)

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Bacterial gene therapy - bactofection is a simple and effective method to deliver plasmid DNA into target tissue. We hypothesize that oral in vivo bactofection can be an interesting approach to influence the course of inflammatory bowel diseases. The aim of this study was to prove the effects of antioxidative and anti-inflammatory bactofection in dextran sulfate sodium (DSS)-treated mice. Attenuated bacteria Salmonella Typhimurium SL7207 carrying plasmids with genes encoding Cu-Zn superoxide dismutase and an N-terminal deletion mutant of monocyte chemoattractant protein-1 were prepared. Male Balb/c mice had ad libitum access to 1% DSS solution in drinking water during 10 days (mild model of colitis). The animals were daily fed with 200 Mio bacteria via gastric gavage during the experiment. Fecal consistency, clinical status, food and water intake were monitored. After 10 days samples were taken and markers of oxidative stress and inflammatory cytokine levels were measured. Colonic tissue was scored histologically by a blinded investigator. DSS treatment significantly increased the levels of inflammatory cytokines and malondialdehyde as a marker of lipoperoxidation in the colon. Anti-inflammatory gene therapy improved the total antioxidative capacity. In comparison with the untreated group, bacterial gene therapy lowered the histological colitis score. Salmonella-mediated antioxidative and anti-inflammatory gene therapy alleviated colitis in mice. The effect seems to be mediated by increased antioxidative status. Further studies will show whether recombinant probiotics expressing therapeutic gene might be used for the therapy of inflammatory bowel diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Salmonella-mediated gene therapy in experimental colitis in mice

Pálffy

Gardlík

Behuliak

et al. 2011

Exp Biol Med (Maywood)

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“… 32 , 33 , 34 , 35 , 36 , 37 In the anti-TNF-α antibody therapy for rheumatoid arthritis or inflammatory bowel syndrome, the target tissue is the articular cavity or intestinal tract. 38 , 39 However, it occasionally induces a compromised host because the drug is systemically administered. 38 Therefore, in the field of molecular therapy, it is crucial that the therapeutic molecule be delivered only to the target tissues and cells.…”

Section: Discussionmentioning

confidence: 99%

Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia

Terashima

Ogawa

Nakae

et al. 2018

Molecular Therapy - Nucleic Acids

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Astrocyte- and microglia-targeting peptides were identified and isolated using phage display technology. A series of procedures, including three cycles of both in vivo and in vitro biopanning, was performed separately in astrocytes and in M1 or M2 microglia, yielding 50–58 phage plaques in each cell type. Analyses of the sequences of this collection identified one candidate homing peptide targeting astrocytes (AS1[C-LNSSQPS-C]) and two candidate homing peptides targeting microglia (MG1[C-HHSSSAR-C] and MG2[C-NTGSPYE-C]). To determine peptide specificity for the target cell in vitro, each peptide was synthesized and introduced into the primary cultures of astrocytes or microglia. Those peptides could bind to the target cells and be selectively taken up by the corresponding cell, namely, astrocytes, M1 microglia, or M2 microglia. To confirm cell-specific gene delivery to M1 microglia, the complexes between peptide MG1 and siRNA-interferon regulatory factor 5 were prepared and intrathecally injected into a mouse model of neuropathic pain. The complexes successfully suppressed hyperalgesia with high efficiency in this neuropathic pain model. Here, we describe a novel gene therapy for the treatment neuropathic pain, which has a high potential to be of clinical relevance. This strategy will ensure the targeted delivery of therapeutic genes while minimizing side effects to non-target tissues or cells.

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“…Current treatment strategies are based upon the combined use of 5‐aminosalicylate and glucocorticosteroid agents, and on immunosuppressive therapy. Antibiotics are also often associated with the medical treatment during active disease 37,38. Recently, chimeric monoclonal antibodies to the proinflammatory cytokine tumor necrosis factor (TNF)‐α proved to be very effective in the treatment of both refractory disease and fistulizing forms of Crohn's disease 39,40…”

Section: Ibd and Gastrointestinal Parasitic Helminthsmentioning

confidence: 99%

Gastrointestinal Parasites

Moreels

Pelckmans

2005

Inflammatory Bowel Diseases

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Crohn's disease and ulcerative colitis are chronic relapsing inflammatory bowel diseases (IBDs). Different pharmacological agents are currently used in several combinations to control the inflammatory process. Recently, antibodies against the proinflammatory cytokine tumor necrosis factor-alpha appeared to be very effective in treating patients with Crohn's disease. However, due to the fact that the pathogen causing IBD is still unknown, no causative treatment is currently available that is able to make the disease disappear. Recently, the hygiene hypothesis of the development of immunological diseases was proposed, stating that raising children in extremely hygienic environments with less exposure to parasite infections may negatively affect the development of the immune system, predisposing them to immunologic diseases such as IBD. This hypothesis is supported by experimental data showing that helminthic parasites protect against T helper (TH) type 1 cell-mediated gastrointestinal inflammations like Crohn's disease. Both TH-2 cells and regulatory T cells may be involved in this immunomodulatory mechanism. Here, we review the experimental and clinical studies in favor of the hygiene hypothesis, opening perspectives on new therapies for IBD.

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Therapy for Crohn disease

Cited by 6 publications

References 74 publications

Salmonella-mediated gene therapy in experimental colitis in mice

Salmonella-mediated gene therapy in experimental colitis in mice

Gene Therapy for Neuropathic Pain through siRNA-IRF5 Gene Delivery with Homing Peptides to Microglia

Gastrointestinal Parasites

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