Treatment of psoriasis with chronic subcutaneous administration of somatostatin analog 201-995 (Sandostatin): I. An open-label pilot study

Camisa, Charles; O’Dorisio, Thomas M.; Maceyko, Ronald F.; Schacht, Gretchen E.; Mekhjian, Hagop S.; Howe, Brent

doi:10.3949/ccjm.57.1.71

Cited by 12 publications

(8 citation statements)

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“…J Invest Dermatol 122: 812 -819, 2004 A role of neurogenic inflammation in the pathogenesis of psoriasis is substantiated by a number of observations: exacerbations during periods of stress, marked proliferation of terminal cutaneous nerves, and upregulation of neuropeptides (SP, VIP, CGRP) in the psoriatic plaques, therapeutic response to neuropeptide-modulating agents such as capsaicin, somatostatin, and peptide T, and clearance of active plaques of psoriasis at the sites of anesthesia following traumatic denervation of cutaneous nerves (Bernstein et al, 1986;Farber et al, 1986Farber et al, , 1991Wallengren et al, 1987;Naukkarinen et al, 1989;Camisa et al, 1990;Leeman et al, 1991;Raychaudhuri and Farber, 1993;Al'Abadie et al, 1995). The unique features of resolution of psoriasis at sites of anesthesia, upregulation of neuropeptides and a marked proliferation of terminal cutaneous nerves in psoriatic plaques, encouraged us to search for the mechanism of neural influence.…”

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confidence: 98%

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

Raychaudhuri¹,

Sanyal²,

Weltman³

et al. 2004

Journal of Investigative Dermatology

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The peripheral nervous system, in addition to its sensory and motor functions, can induce a local inflammatory response known as neurogenic inflammation. This phenomenon plays a critical role in several inflammatory diseases, e.g., asthma, atopy, rheumatoid arthritis, psoriasis, and ulcerative colitis. Neurogenic inflammation and the role of nerve growth factor (NGF) have been extensively studied in psoriasis. There are increased levels of NGF in the keratinocytes and upregulation of NGF receptor (NGF-R) in the cutaneous nerves of psoriatic plaques. NGF can influence all the salient pathologic events noticed in psoriasis such as proliferation of keratinocytes, angiogenesis, T cell activation, expression of adhesion molecules, proliferation of cutaneous nerves, and upregulation of neuropeptides. In this double-blinded, placebo-controlled study, we addressed the role of NGF/NGF-R in psoriasis in an in vivo system using the severe combined immunodeficient (SCID) mouse-human skin model of psoriasis. The transplanted psoriatic plaques on the SCID mice (n=12) were treated with K252a, a high-affinity NGF receptor blocker. Psoriasis significantly improved following 2 wk of therapy. The length of the rete pegs changed from 308.57+/-98.72 to 164.64+/-46.78 microm (p<0.01, Student's t test). A similar improvement of psoriasis was observed by directly inhibiting NGF with NGF-neutralizing antibody. NGF-neutralizing antibody in normal saline at 10 ng (n=4) and 20 ng (n=4) per kilogram of body weight doses were used. Both doses of NGF-neutralizing antibody reduced rete peg lengths significantly, e.g., from 298.5+/-42.69 to 150.52+/-32.93 microm (p<0.05, Student's t test). This study provides evidence for the role of NGF and its high-affinity receptor in the pathogenesis of psoriasis and insights to develop novel therapeutic modalities.

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confidence: 98%

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

Raychaudhuri¹,

Sanyal²,

Weltman³

et al. 2004

Journal of Investigative Dermatology

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“…Accepted for publication January 11, 2008. matostatin, 11 peptide T, 12 and clearance of active plaques of psoriasis at the sites of anesthesia after traumatic denervation of cutaneous nerves. 5,10 The unique features of resolution of psoriasis at sites of anesthesia, up-regulation of neuropeptides, and a marked proliferation of terminal cutaneous nerves in psoriatic plaques 6 -8 encouraged us to search for the mechanism of neural influence.…”

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confidence: 99%

Revisiting the Koebner Phenomenon

Raychaudhuri

Jiang

Raychaudhuri

2008

The American Journal of Pathology

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Nerve growth factor (NGF) influences the key pathological events of psoriasis: keratinocyte proliferation, angiogenesis, and T-cell activation. We have systematically examined the kinetics of NGF expression, keratinocyte proliferation, and migration of T lymphocytes in the epidermis in Koebner-induced developing psoriatic plaques. In skin traumatized by the tape-stripping method (n ‫؍‬ 12), a marked up-regulation of NGF in Koebner-positive lesions (n ‫؍‬ 7) was observed 24 hours after trauma. Synthesis of NGF reached its maximum level in the 2nd week. Furthermore, cultured keratinocytes from nonlesional skin of psoriasis patients produced 10 times higher levels of NGF compared with keratinocytes from healthy individuals. To substantiate the in vivo effect of NGF secreted by keratinocytes in psoriatic plaques, we studied psoriatic plaques and normal human skin in a SCID-human skin xenograft model. The transplanted psoriatic plaques demonstrated marked proliferation of NGF-R (p75)-positive nerve fibers compared with only a few nerves in the transplanted normal human skin. Our results demonstrate that 1) in a developing psoriatic lesion, up-regulation of NGF together with keratinocyte proliferation are early events and precede epidermotropism of T lymphocytes; 2) keratinocytes in patients with psoriasis are primed to produce elevated levels of NGF; and 3) NGF synthesized by these keratinocytes is functionally active.

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“…It was shown that non-lesional skin can be converted to active psoriatic plaque not only by superantigen activated autologous lymphomononuclear cells [66] but also T cells activated with substance P (SP) and nerve growth factor (NGF). [68] Apart from neuropeptide-induced T cell activation, stress-induced onset and exacerbation of psoriasis, [69] upregulation of neuropeptides with proliferation of terminal cutaneous nerves in psoriatic plaques, [70][71][72] positive response to capsaicin, somatostatin and peptide T, [73][74][75][76] and disappearance of active plaques at sites of local anesthesia [77] supported the role of neurogenic inflammation in psoriasis.…”

Section: Exploring Pathogenesis Of Psoriasismentioning

confidence: 98%

“…Thus the SCID model has proved to be a very effective model to explore the role of neurogenic inflammation in psoriasis and has opened a door to the development of drugs targeting the NGF/NGF-R system. [73,74,[81][82][83] In psoriasis there is increased expression of endothelial cell adhesion molecules (E-selectin, ICAM, VCAM), [84][85][86][87] angiogenesis with upregulation of endothelial cell-stimulating angiogenesis factor (ESAF) and VEGF [88,89] activated T-cells (CD4, CD8, NK cells) infiltrates [90][91][92][93] neutrophils (Munro's and Kogoji microabscess), mast cells, [93,94] upregulation of chemokines such as IL-8, RANTES, fractalkine, [17,[95][96][97] and neuropeptides. [71,72,98,99] Likewise, the transplanted psoriatic plaques in SCID mice, demonstrate upregulation of molecules like p38 MAPK, STAT3, ICAM, CXCR3, fractalkine, IL-8, CD3, CD4, CD8, CD40, CD80, CD86, HLA-DR, OX-40R, K16, Ki67, SP, NGF, and NGF-R. Upregulation of CD80/CD86 supports the role of CD28/B7 co-stimulatory cascades in psoriatic inflammation.…”

Section: Exploring Pathogenesis Of Psoriasismentioning

confidence: 98%

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

Kundu-Raychaudhuri

Datta-Mitra

Abria

et al. 2014

Indian J Dermatol Venereol Leprol

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Psoriasis is a multifactorial chronic inflammatory disease. Research into the pathogenesis of this disease is hindered by the lack of a proper animal model. Over the past two decades, many scientists were involved in the development of animal models that nearly mirror the immunopathogenesis of psoriasis. One such model, which has opened doors to the study of molecular complexities of psoriasis as well as its treatment, is the severe combined immunodeficiency (SCID) mouse-human skin chimera model. This model not only mirrors the clinical and histopathological features of psoriasis but also help in the study of cell proliferation, angiogenesis, function of T cells, neurogenic inflammation and cytokines involved in inflammatory reactions. In this article, we have reviewed the prospects and the limitations of the SCID mouse model of psoriasis.

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Treatment of psoriasis with chronic subcutaneous administration of somatostatin analog 201-995 (Sandostatin): I. An open-label pilot study

Cited by 12 publications

References 0 publications

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

K252a, a High-Affinity Nerve Growth Factor Receptor Blocker, Improves Psoriasis: An In Vivo Study Using the Severe Combined Immunodeficient Mouse–Human Skin Model

Revisiting the Koebner Phenomenon

Severe combined immunodeficiency mouse-psoriatic human skin xenograft model: A modern tool connecting bench to bedside

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