Peptide T improves psoriasis when infused into lesions in nanogram amounts

Farber, Eugene M.; Cohen, Ellis N.; Trozak, Daniel J.; Wilkinson, David

doi:10.1016/0190-9622(91)70249-2

Cited by 42 publications

(21 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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.…”

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…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.…”

mentioning

confidence: 99%

Revisiting the Koebner Phenomenon

Raychaudhuri

Jiang

Raychaudhuri

2008

The American Journal of Pathology

View full text Add to dashboard Cite

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.

show abstract

“…This hypothesis was subsequently used for 3D data base search, obtaining several hits, among which the natural product amigdalin was found. The disaccharide derivative was tested for its ability to produce chemotaxis on human monocytes and was found to exhibit a maximum chemotactic index of 1.35 at 0.1 nM, compared to a maximum of 1.60 exhibited by (4)(5)(6)(7)(8)peptide T at the same concentration. However, an inspection of its superposition with the bioactive form of peptide T suggested simple modifi-cations to improve its activity.…”

Section: Resultsmentioning

confidence: 99%

“…It has also proven quite potent in triggering human monocyte chernotaxis through the CD4/T4 antigen [2]. Furthermore, pharmacological studies on peptide T and its analogs show them to be very promising for their potential applicability as therapeutic agents for the treatment of neuropsychometric symptoms in AIDS patients [3] and psoriasis [4].…”

Section: Introductionmentioning

confidence: 98%

A proposed bioactive form of peptide T and the design of peptidomimetics

et al. 1998

View full text Add to dashboard Cite

SummaryPeptide T is a non-natural octapeptide of sequence Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr, taken from the sequence of the protein gp120 of HIV. The peptide has been shown to bind competitively to the CD4 receptors of the helper/inducer lymphocytes T. The peptide is presently used for the treatment of AIDS-associated dementia and has been proven useful for the treatment of psoriasis. Using molecular modeling procedures, we studied the conformational profile of this peptide as well as those of several active and inactive analogs. The analysis of these results gave rise to the proposal of a bioactive conformation of the peptide, which can be described as a pseudo/~-turn structure, involving the last four residues at the C-terminus of the peptide. The secondary structure is stabilized by a hydrogen bond between the hydroxyl hydrogen of the side chain of Thr 5 and the carbonyl oxygen of Tyr 7. From the bioactive form and different structure-activity relationship studies, a pharmacophore was proposed. This hypothesis was used to search on several 3D data bases. One of the hits obtained was the natural compound amigdalin, which was tested and exhibited moderate activity.

show abstract

Peptide T improves psoriasis when infused into lesions in nanogram amounts

Cited by 42 publications

References 11 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

A proposed bioactive form of peptide T and the design of peptidomimetics

Contact Info

Product

Resources

About