A phase 2a, open-label pilot study of the galectin-3 inhibitor GR-MD-02 for the treatment of moderate-to-severe plaque psoriasis

Ritchie, Simon; Neal, Danielle; Shlevin, Harold; Allgood, Adam; Traber, Peter G.

doi:10.1016/j.jaad.2017.05.055

Cited by 15 publications

(11 citation statements)

References 3 publications

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“…The same drug was used to study potential inhibition of inflammation in psoriasis subjects (only five subjects and no control group). Interestingly, patients infused with GR-MD-02 biweekly 13 times showed an average of >50% reduction in the Psoriasis Area Severity Index [ 110 ]. However, the lack of control subjects, the few subjects included, and the short time frame studied suggest that further studies must be conducted before one can conclude that the galectin-3 inhibitor has potential for treating psoriasis.…”

Section: Main Textmentioning

confidence: 99%

The Role of Galectins as Modulators of Metabolism and Inflammation

Brinchmann

Patel

Iversen

2018

Mediators of Inflammation

113

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Galectins are β-galcotosid-binding lectins. The function of galectins varies with their tissue-specific and subcellular location, and their binding to carbohydrates makes them key players in several intra- and extracellular processes where they bind to glycosylated proteins and lipids. In humans, there are 12 identified galectins, some with tissue-specific distribution. Galectins are found inside cells and in the nucleus, cytosol, and organelles, as well as extracellularly. Galectin-1, -2, -3, -4, -7, -8, -9, and -12 can all induce T-cell apoptosis and modulate inflammation. In the context of metabolic control and loss of the same in, for example, diabetes, galectin-1, -2, -3, -9, and -12 are especially interesting. This review presents information on galectins relevant to the control of inflammation and metabolism and the potential to target galectins for therapeutic purposes.

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Section: Main Textmentioning

confidence: 99%

The Role of Galectins as Modulators of Metabolism and Inflammation

Brinchmann

Patel

Iversen

2018

Mediators of Inflammation

113

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“…Ritchie et al [88] found that galectin-3 participates in cell proliferation, differentiation, and apoptosis and has a central role in skin disease (dermatitis and some skin cancers) as its decrease leads to changes in keratinocyte functioning and characterization through the JNK pathway.…”

Section: Association Between Some Obesity Biomarkers and Psoriasismentioning

confidence: 99%

Biomarkers of Inflammation in Obesity-Psoriatic Patients

Rodríguez-Cerdeira

Cordeiro-Rodríguez

Carnero-Gregorio

et al. 2019

Mediators of Inflammation

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Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin- (IL-) 6 and tumour necrosis factor-α. In psoriasis, due to the proliferation of Th1, Th17, and Th22 cells, IL-22, among others, is produced in addition to the abovementioned cytokines. With respect to leptin and resistin, both of these adipokines are present in high levels in obese persons with psoriasis. Further, the plasma levels of leptin and resistin are related to the severity of psoriasis. These results strongly suggest that obesity, through proinflammatory pathways, is a predisposing factor to the development of psoriasis and that obesity aggravates existing psoriasis. Different inflammatory biomarkers link psoriasis and obesity. In this paper, the most important ones are described.

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“…Currently, many clinical trials are ongoing on new therapies targeting galectins or development of galectins as biomarkers for cardiovascular diseases and cancers. Although clinical trials of galectin inhibitors on skin diseases are still very limited, a recent trial has demonstrated the potential therapeutic effect of a novel galectin‐3 inhibitor GR‐MD‐02 in the treatment of psoriasis . Future studies to clarify the in vivo role of galectins in skin pathogenesis may shed light on the design of novel galectin‐based therapies for skin diseases.…”

Section: Discussionmentioning

confidence: 99%

The expression and function of galectins in skin physiology and pathology

Liu

2018

Experimental Dermatology

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The galectin family comprises β-galactoside-binding proteins widely expressed in many organisms. There are at least 16 family members, which can be classified into three groups based on their carbohydrate-recognition domains. Pleiotropic functions of different galectins in physiological and pathological processes through extracellular or intracellular actions have been revealed. In the skin, galectins are expressed in a variety of cells, including keratinocytes, melanocytes, fibroblasts, dendritic cells, lymphocytes, macrophages and endothelial cells. Expression of specific galectins is reported to affect cell status, such as activation or death, and regulate the interaction between different cell types or between cells and the extracellular matrix. In vitro cellular studies, in vivo animal studies and studies of human clinical material have revealed the pathophysiologic roles of galectins in the skin. The pathogenesis of diverse non-malignant skin disorders, such as atopic dermatitis, psoriasis, contact dermatitis and wound healing, as well as skin cancers, such as melanoma, squamous cell carcinoma, basal cell carcinoma and cutaneous haematologic malignancy can be regulated by different galectins. Revelation of biological roles of galectins in skin may pave the way to future development of galectin-based therapeutic strategies for skin diseases.

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A phase 2a, open-label pilot study of the galectin-3 inhibitor GR-MD-02 for the treatment of moderate-to-severe plaque psoriasis

Cited by 15 publications

References 3 publications

The Role of Galectins as Modulators of Metabolism and Inflammation

The Role of Galectins as Modulators of Metabolism and Inflammation

Biomarkers of Inflammation in Obesity-Psoriatic Patients

The expression and function of galectins in skin physiology and pathology

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