Methods and compositions for treating asthma and allergic diseases
The present invention relates to the allergy field. Several independent groups have recently investigated the implication of PCSK9 on inflammation and sepsis but none of them have determined 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.
1. A method for assessing or predicting severity of an allergic disease in a subject, comprising
i) determining a PCSK9 level in a biological sample obtained from the subject,
ii) comparing the level determined at step i) with a predetermined reference value,
iii) concluding that the subject has or is susceptible to have a severe allergic disease when the level of PCSK9 is higher than the predetermined reference value, wherein the allergic disease is selected from the group consisting of a food allergy, allergic rhinitis and asthma, and
iv) administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a PCSK9 inhibitor.
2. The method according to claim 1 wherein the biological sample is a blood sample and/or a bronchoscopy and bronchoalveolar lavage (BAL) sample.
3. The method of claim 1 wherein the biological sample is a peripheral blood mononuclear cell (PBMC) sample.
4. The method according to claim 1 wherein the PCSK9 level is measured by ELISA.
5. The method of claim 1 , wherein the inhibitor of PCSK9 is selected from the group consisting of alirocumab, evolocumab and bococizumab.
6. A method of treating allergic disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an inhibitor of PCSK9, wherein the allergic disease is asthma or food allergy, and wherein the method comprises predicting whether the subject is at risk of having the allergic disease by
i) determining the PCSK9 level in a biological sample obtained from the subject,
ii) comparing the level determined at step i) with a predetermined reference value
iii) concluding that the subject has or is susceptible to have severe allergic disease when the level of PCSK9 is higher than the predetermined reference value, and
iv) administering the therapeutically effective amount of the inhibitor of PCSK9.
7. The method according to claim 6 , wherein the inhibitor is an antibody.
8. The method according to claim 6 , wherein the inhibitor is alirocumab, evolocumab or bococizumab.
9. A method of treating or inhibiting severe asthma or food allergy in a subject in need thereof, comprising
i) measuring a PCSK9 level in a biological sample obtained from the subject,
ii) comparing the level determined at step i) with a predetermined reference value
iii) determining that the subject has or is susceptible to have severe asthma or food allergy when the level of PCSK9 is higher than the predetermined reference value, and
iv) administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an inhibitor of PCSK9 selected from the group consisting of alirocumab, evolocumab and bococizumab.
10. The method of claim 9 , wherein the pharmaceutical composition further comprises at least one β-adrenoceptor agonist selected from the group consisting of a corticosteroid, a bronchodilator, a methylxanthine, an anti-leukotriene, an interleukin inhibitor a mast cell stabilizer and an allergen immunotherapy.
11. The method according to claim 6 , wherein the allergic disease is a food allergy.