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Methods and compositions for treating asthma and allergic diseases

A technology for allergic diseases and asthma, applied in the field of allergies, can solve problems such as no certain impact

Pending Publication Date: 2021-04-13
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Several independent groups have recently studied the impact of PCSK9 on sepsis, but none of them have established its impact on allergy and / or asthma, which are a global health burden

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  • Methods and compositions for treating asthma and allergic diseases
  • Methods and compositions for treating asthma and allergic diseases
  • Methods and compositions for treating asthma and allergic diseases

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Embodiment Construction

[0009] The inventors have obtained preliminary data in wild-type (PCSK9+ / +) or PCSK9-deficient mice (PCSK9- / -) and found that PCSK9 deficiency significantly increased spleen , percentage of regulatory T cells in mesenteric lymph nodes and Peyer's patches. Interestingly, altered activation of these cells in allergy is thought to be critical in the development of chronic inflammation. Furthermore, the inventors have discovered the effect of allergic challenge of primary human bronchial epithelial cells on PCSK9 expression and secretion. Very interestingly, their first results by Q-PCR showed that house dust mite (HDM) allergens and LPS increased PCSK9 mRNA levels. Likewise, HDM caused a strong increase in intracellular PCSK9 protein content. A trend towards increased intracellular PCSK9 was also observed (+53%) when the cells were cultured with LPS. It also found that the concentration of PCSK9 in the medium was increased after HDM or LPS treatment.

[0010] Therefore, the i...

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Abstract

The present invention relates to allergy field. Several independent groups have recently investigated the implication of PCSK9 on inflammation and sepsis but none of them have determine its impact on allergies and / or asthma which is a global health burden. Inventors have obtained preliminary data on wild-type (PCSK9+ / +) or PCSK9-deficient mice (PCSK9- / -) and shown that, under basal condition and in the absence of a particular stimulus, PCSK9 deficiency significantly increases the percentage of regulatory T cells in the spleen, the mesenteric lymph nodes and Peyer's patches. Moreover, inventors have shown the effect of allergic challenge on primary human bronchial epithelial cells on PCSK9 expression and secretion. Very interestingly, their first results obtained by Q-PCR showed that HDM and LPS increase PCSK9 mRNA levels. Accordingly, the present invention relates to inhibitors of PCSK9 for use in the treatment of asthma and / or allergic disease, such as food allergy.

Description

technical field [0001] The present invention relates to the field of allergy. More specifically, the present invention relates to methods and compositions for the treatment of asthma and allergic diseases such as food allergies. Background technique [0002] PCSK9 (proprotein convertase subtilisin kexin type 9) is a key regulator of cholesterol metabolism, and PCSK9 inhibitors have been developed to treat hypercholesterolemia and cardiovascular diseases. [0003] PCSK9 was discovered in 2003 in patients with autosomal dominant hypercholesterolemia (1), and its canonical role as a natural inhibitor of the low-density lipoprotein receptor (LDLR) was quickly established (2). After autophagy in the endoplasmic reticulum, PCSK9 is secreted by the liver into a mature form in the blood. PCSK9 binds to the extracellular domain of LDLR and interferes with LDLR trafficking by promoting its lysosomal degradation rather than recycling to the membrane. Genetic studies have further dem...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61P37/08A61K39/395A61K31/713C12N15/113A61P11/06
CPCA61P11/06A61P37/08C12N15/1137C12N2310/11C12N2310/14C12N2310/531A61K31/00G01N2333/956G01N33/6893G01N2800/122C07K16/40C07K2317/76G01N2333/96433G01N2800/24G01N2800/56
Inventor B·卡里乌A·马尼昂G·布绍C·勒迈
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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