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Use of cgrp antagonist compounds for treatment of psoriasis

a technology of psoriasis and cgrp, which is applied in the field of psoriasis treatment with cgrp antagonist compounds, can solve the problems of limited success in clearing the skin for short periods of time, skin redness, and the reason for the treatment's effectiveness is not yet clearly understood

Inactive Publication Date: 2011-06-23
SVEINSSON BIRKIR
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention proposes that the overrepresentation of calcitonin gene related peptide (CGRP) is responsible for the pathological phenomena of psoriasis, such as hyperproliferation, increased number of T-cells, increased blood flow, and localization of lesions. It also explains the therapeutic effect of sunlight and the negative effect of streptococcal infection on psoriasis. The invention proposes that by regulating CGRP through the use of CGRP antagonists, the disease can be treated and prevented. The invention is based on the observation that changing the level of CGRP can affect the disease."

Problems solved by technology

Additionally, the capillaries become tortuous and dilated and an inflammatory reaction occurs, so that the skin reddens.
There have been many attempts to treat the disease, and several topical and systemic treatments for psoriasis which inhibit cell division have been tried, with limited success in clearing the skin for short periods of time.
Yet, the reason why these treatments work is not yet clearly understood.
Certain observations support this notion, for example, smoking is known to increase likelihood of psoriasis, and smoking is also known to cause defects in tryptase in lungs.
Such compounds however, have not to my knowledge been suggested for treatment of psoriasis.

Method used

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  • Use of cgrp antagonist compounds for treatment of psoriasis
  • Use of cgrp antagonist compounds for treatment of psoriasis
  • Use of cgrp antagonist compounds for treatment of psoriasis

Examples

Experimental program
Comparison scheme
Effect test

example 1

Case Study: Possible Involvement of Neuropeptidergic Sensory Nerves in AA

[0103]A recent study by R. Rossi et al. (Rossi, R. et al. Neuroreport, 8, 1135-1138 1997) indicated, that patients with AA have lower basal blood flow. It was further shown that CGRP and SP (substance P) levels but not VIP (vasoactive intestinal peptide) are decreased in scalp biopsies of patients affected by AA. Reaction to stimuli is altered, such that a greater and more prolonged vasodilation in response to intradermal CGRP is observed in alopecic scalp than in controls. This is suggested by the authors of the study to indicate CGRP receptor hypersensitivity, due to a previous reduction in the amount of the neuropeptide present.

example 2

Clinical Observation of a Patient with AA and Psoriasis

[0104]A clinical observation of a Down's syndrome patient with AA and psoriasis showed that the patient had M covering an area from one ear to the other through his occipital region. His whole scalp was covered with psoriasis except for the area where he had AA (see FIGS. 1a &b). In those areas the scalp was clinically normal. The patient had psoriasis on his elbows and a strong family history of psoriasis.

[0105]The observation strongly indicates that there is an inverse relationship between the two diseases, which has to my knowledge not been described before. In conjunction with the results of Example 1 that CGRP levels are lower in AA areas, this further supports the notion that CGRP is a causative agent in psoriasis.

example 3

Clinical Observation of Psoriasis Patients Treated with UVB Therapy

[0106]Patients receiving UVB treatment according to standard clinical practice were observed and interviewed. It was noticed that several patients experienced transient worsening of psoriasis after their first treatment sessions, in the very first days after initiating treatment, before they begin to get better. Worsening was defined as flare-up or increased size of existing lesions or appearance of new ones.

[0107]Out of 95 patients interviewed, 38 said they had experienced worsening of their psoriasis. 21 got new lesions, most often lasting for 1 or 2 days. These lesions were often described as small, thin and red macules. 17 patients noticed a short worsening period of already existing psoriasis lesions. These symptoms were noted typically within 24-48 hours after first treatment. All patients, however, benefited from the treatment, i.e., received overall improvement of psoriasis over a longer time.

[0108]I postulat...

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Abstract

The invention provides methods and compositions for treating, preventing and / or remedying psoriasis, based on compounds that have a calcitonin-related gene peptide (CGRP) antagonistic effect. Methods are also disclosed for identifying compounds with CGRP antagonist activity which thereby are suitable candidate compounds for treating psoriasis.

Description

FIELD OF THE INVENTION[0001]This invention relates to compositions and compounds that are CGRP antagonists, or reduces its activity for use in particular for treating and or preventing psoriasis.BACKGROUND[0002]Psoriasis is a chronic skin disorder that afflicts about 2 percent of the population. The disease is associated with the rapid turnover of skin cells (hyperproliferation) accompanied by a loss of differentiation so that silvery white scales form on the surface of the skin. Additionally, the capillaries become tortuous and dilated and an inflammatory reaction occurs, so that the skin reddens. The elevated silvery white scales on a contrasting red background produce the unsightly lesions characteristic of psoriasis. Psoriasis most commonly appears on the scalp, knees, elbows, hands and feet, but can affect any part of the skin. The cause of the disease is unknown, though it is believed to have a genetic component, and it has been suggested to be a T-cell mediated autoimmune ski...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K38/16A61K38/48A61K31/727A61P17/06A61K31/00A61K31/166A61K31/517A61K38/22G01N33/50G01N33/74
CPCA61K31/00G01N33/566A61K31/517A61K31/727A61K38/225A61K38/482G01N33/5008G01N33/502G01N33/5044G01N33/5088G01N33/74G01N2333/5753A61K31/506C07K16/26A61K31/166A61P17/00A61P17/06A61K9/107A61K47/44A61K38/23A61K31/4184A61P17/02A61K9/0014
Inventor SVEINSSON, BIRKIR
Owner SVEINSSON BIRKIR