Yersinia outer protein m (YOPM) in the treatment of psoriasis

Abstract

The present invention relates to the use of Yersinia outer protein M (YopM)in the prevention and / or treatment of psoriasis by cutaneous, intradermalor subcutaneous administration. In particular, the present invention relates to the use of YopM in the treatment of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, erythrodermic psoriasis, arthritis psoriasis.

Description

1. FIELD OF THE INVENTION[0001]The present invention relates to the use of Yersinia outer protein M (YopM) in the prevention and / or treatment of psoriasis by cutaneous, intradermal or subcutaneous administration.2. BACKGROUND ART[0002]The YopM protein consists of two amino terminal helices followed by variable numbers of an approximately 20 amino acid leucine-rich repeat (LRR) motif (12-20 LRR among different Yersinia strains), forming a horseshoe-shaped protein. The LRR, which have been implicated in protein-protein interactions, make up most of YopM (FIG. 1).[0003]Besides protein-protein interactions with serum proteins such as a-thrombin and α1-antitrypsin (Hines et al., 2000; Heusipp et al., 2006) and a scaffolding function of YopM with two cytoplasmic kinases, RSK1 and PRK2 (McDonald et al., 2003) the molecular function of YopM during infection is only poorly understood.[0004]The fact that yopM mutants of Y. enterocolitica and Y. pestis cannot establish a systemic infection in ...

AI Technical Summary

Benefits of technology

The present inventors have discovered that Yersinia outer protein M (YopM) can prevent and treat psoriasis when administered through cutaneous, intradermal, or subcutaneous routes. This method of treatment is preferred over the intra-peritoneal route as it reduces the risk of side effects. Additionally, the inventors found that YopM stayed in the epidermis, dermis, and subcutis and didn't enter the systemic distribution. This suggests that an epicutaneous treatment with YopM is more effective and safer than a sub-cutaneous injection. Therefore, the cutaneous administration route is the preferred method of the present invention.

Problems solved by technology

How YopM interferes with the signalling pathways of the proinflammatory cytokines is just speculative and has not been investigated.

The pathogenesis of psoriasis is complex and not clearly understood.

This further activates dendritic cells which in turn leads to inflammation.

Inverse psoriasis is subject to irritation from rubbing and sweating because of its location in skin folds and tender areas.

It can be more troublesome in overweight people and those with deep skin folds.

The reddening and shedding of the skin are often accompanied by severe itching and pain, heart rate increase, and fluctuating body temperature.

Erythrodermic psoriasis causes protein and fluid loss that can lead to severe illness.

The condition may also bring on infection, pneumonia and congestive heart failure.

A common disadvantage (besides their side effects) of all drugs currently available for treating this primarily cutaneous disease is that they are only effective when given systemically but are largely ineffective when applied topically because of poor absorption.

The systemic treatments that are available to treat psoriasis and psoriatic arthritis are associated with significant short- and long-term side effects.

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