METHODS AND COMPOSITIONS FOR TREATMENT OF NLRP3 INFLAMMASOME MEDIATED IL-1BETA DEPENDENT DISORDERS
The present invention relates to a PAK-1 and/or PAK-2 inhibitor for use in the treatment of NLRP3 inflammasome mediated IL-1beta dependent disorders in a subject in need thereof. Inventors invalidated PAK-1 and/or PAK-2 in BMDM by transfecting siRNA targeting either PAK-1 and/or PAK-2 (PAK-3 is predominantly expressed in the brain). After 72 hours of siRNA expression, cells were stimulated by LPS and the CNF1 toxin for 8 hours. They observed that cells invalidated for PAK-1 had a reduced Caspase-1 activation compared to the control cells or cells invalidated for PAK-2. Similar results were observed when the IL-1β maturation was monitored. Confirming this data, the use of PAK-1 inhibitors (IPA-3 and FRAX597) were sufficient to block the IL-1β maturation observed in macrophages treated with LPS and CNF1 as well as Caspase-1 activation measured using FAM-FLICA..
| Medienart: |
|
|---|
Patent| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Europäisches Patentamt - (2022) vom: 23. Feb. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
BOYER LAURENT [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Anmerkungen: |
Source: www.epo.org (no modifications made), First posted: 2022-02-23, Last update posted on www.tib.eu: 2022-10-07, Last updated: 2023-02-09 |
|---|
| Patentnummer: |
EP3956446 |
|---|
| Förderinstitution / Projekttitel: |
|
|---|
| PPN (Katalog-ID): |
EPA014015021 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | EPA014015021 | ||
| 003 | DE-627 | ||
| 005 | 20230503183956.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230215s2022 xx |||||o 00| ||eng c | ||
| 035 | |a (DE-627)EPA014015021 | ||
| 035 | |a (EPA)EP3956446 | ||
| 035 | |a (EPA)66439949 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 0 | |a BOYER LAURENT |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a METHODS AND COMPOSITIONS FOR TREATMENT OF NLRP3 INFLAMMASOME MEDIATED IL-1BETA DEPENDENT DISORDERS |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Source: www.epo.org (no modifications made), First posted: 2022-02-23, Last update posted on www.tib.eu: 2022-10-07, Last updated: 2023-02-09 | ||
| 520 | |a The present invention relates to a PAK-1 and/or PAK-2 inhibitor for use in the treatment of NLRP3 inflammasome mediated IL-1beta dependent disorders in a subject in need thereof. Inventors invalidated PAK-1 and/or PAK-2 in BMDM by transfecting siRNA targeting either PAK-1 and/or PAK-2 (PAK-3 is predominantly expressed in the brain). After 72 hours of siRNA expression, cells were stimulated by LPS and the CNF1 toxin for 8 hours. They observed that cells invalidated for PAK-1 had a reduced Caspase-1 activation compared to the control cells or cells invalidated for PAK-2. Similar results were observed when the IL-1β maturation was monitored. Confirming this data, the use of PAK-1 inhibitors (IPA-3 and FRAX597) were sufficient to block the IL-1β maturation observed in macrophages treated with LPS and CNF1 as well as Caspase-1 activation measured using FAM-FLICA. | ||
| 650 | 4 | |a C12N: Microorganisms or enzymes; compositions thereof; propagating, preserving, or maintaining microorganisms; mutation or genetic engineering; culture media (microbiological testing media c12q0001000000) | |
| 650 | 4 | |a che | |
| 650 | 4 | |a A61K: Preparations for medical, dental, or toilet purposes (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms a61j0003000000;chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles a61l; soap compositions c11d) | |
| 650 | 4 | |a bio | |
| 650 | 4 | |a 615 | |
| 700 | 0 | |a DUFIES OCÉANE |4 aut | |
| 700 | 0 | |a DOYE ANNE |4 aut | |
| 700 | 0 | |a COURJON JOHAN-VICTOR |4 aut | |
| 700 | 0 | |a LOUBATIER CÉLINE |4 aut | |
| 700 | 0 | |a MICHEL GRÉGORY |4 aut | |
| 700 | 0 | |a TORRE CÉDRIC |4 aut | |
| 700 | 0 | |a VISVIKIS ORANE |4 aut | |
| 700 | 0 | |a MUNRO PATRICK |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Europäisches Patentamt |g (2022) vom: 23. Feb. |
| 773 | 1 | 8 | |g year:2022 |g day:23 |g month:02 |
| 856 | 4 | 0 | |u https://worldwide.espacenet.com/patent/search/family/66439949/publication/EP3956446A1?q=EP3956446 |z kostenfrei |3 Volltext |
| 912 | |a GBV_EPA | ||
| 912 | |a SSG-OLC-PHA | ||
| 936 | u | w | |j 2022 |b 23 |c 02 |
| 951 | |a AR | ||
| 952 | |j 2022 |b 23 |c 02 | ||