Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders

a technology of senescent cells and compositions, applied in the field of methods for treating and prophylaxis of senescent cellassociated diseases and disorders, can solve the problems of ineffective treatment of cancer dose of senolytic agents administered during each treatment cycle, and achieve the effects of promoting the death of senescent cells, and reducing the likelihood of occurren

Inactive Publication Date: 2017-07-13
MAYO FOUND FOR MEDICAL EDUCATION & RES +3
View PDF5 Cites 18 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent text describes a method for treating diseases associated with senescent cells, which are cells that have stopped dividing and are associated with aging. The method involves using a drug called a senolytic agent that targets specific signaling pathways in the senescent cells to promote their death. The drug can be given once every few months, and the targeted diseases include cardiovascular diseases, inflammatory diseases, pulmonary diseases, neurological diseases, chemotherapy side effects, and metastasis. The technical effect of the patent is to provide a potential therapy for age-related diseases and disorders.

Problems solved by technology

In a specific embodiment, the senolytic agent is an MDM2 inhibitor or is an inhibitor of one or more BCL-2 anti-apoptotic protein family members wherein the inhibitor inhibits at least BCL-xL and is cytotoxic to cancer cells, the total dose of the senolytic agent administered during each treatment cycle is an amount ineffective for treating a cancer.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
  • Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders
  • Methods and compositions for killing senescent cells and for treating senescence-associated diseases and disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

In Vitro Cell Assays for Determining Senolytic Activity of Nutlin-3A

[0366]Foreskin fibroblast cell lines HCA2 and BJ, lung fibroblast cell line IMR90, and mouse embryonic fibroblasts were seeded in six-well plates and induced to senesce with 10 Gy of ionizing radiation (IR) or a 24 hr treatment with doxorubicin (Doxo). Senescent phenotype was allowed to develop for at least 7 days, at which point a cell count was made to determine the baseline number of cells. Nutlin-3a treatment was then initiated for a period of at least 9 days. Media alone or media with drug as appropriate was refreshed at least every three days. At the end of the assay time period, cells are counted. Each condition was seeded in three plate wells and counted independently. Initial cell count serves as a control to determine the induction of senescence, as compared to the last day count without nutlin treatment. Initial non-senescent cell count serves as a proxy to determine Nutlin-3a toxicity. FIG. 1 shows a sch...

example 2

Nutlin-3A Treatment of P16-3MR Transgenic Mice

[0371]The capability of Nutlin-3a to remove senescent cells in vivo was determined in transgenic p16-3MR mice (see, e.g., International Application Publication No. WO2013 / 090645). A schematic of the experimental protocol is provided in FIG. 6. The transgenic mouse comprises a p16Ink4a promoter operatively linked to a trimodal fusion protein for detecting senescent cells and for selective clearance of senescent cells in these transgenic mice, which is illustrated in FIG. 7. The promoter, p16Ink4a, which is transcriptionally active in senescent cells but not in non-senescent cells (see, e.g., Wang et al., J. Biol. Chem. 276:48655-61 (2001); Baker et al., Nature 479:232-36 (2011)), was engineered into a nucleic acid construct. 3MR (tri-modality reporter) is a fusion protein containing functional domains of a synthetic Renilla luciferase (LUC), monomeric red fluorescence protein (mRFP), and truncated herpes simplex virus (HSV)-1 thymidine ki...

example 3

Mdm2 Inhibitor Removes Senescent Cells with Established SASP

[0378]Primary human fibroblast (IMR90) cells were induced to senesce by applying 10Gy of irradiation. Seven days after irradiation (Day 0), cells were treated with 10 μM Nutlin-3a or vehicle (DMSO) for nine days (Day 9). The drug or vehicle was refreshed every three days. Drug / vehicle was removed at Day 9 and the cells were cultured for an additional three days (Day 12). Cells were then fixed with 4% paraformaldehyde and stained by immunofluorescence with a specific anti-IL-6 antibody (R&D, AF-206-NA). Cells were counterstained with DAPI for nuclear visualization. The percent IL-6 positive cells is illustrated in FIG. 12A. An example of IL-6 positive cell immunofluorescence is shown in FIG. 12B. IL-6 positive cells were determined in an unbiased manner using CellProfiler software. Three different cultures were assessed. Non-senescent cells had no detectable cells IL-6 production while senescent cells were about 8% positive ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a continuation of U.S. patent application Ser. No. 15 / 114,762 (pending), filed Jul. 27, 2016, which is the U.S. National Stage of PCT / US2015 / 013387, filed Jan. 28, 2015; which claims the priority benefit of U.S. Provisional Application 62 / 061,629, filed Oct. 8, 2014, U.S. Provisional Application 62 / 061,627, filed Oct. 8, 2014, U.S. Provisional Application 62 / 057,828, filed Sep. 30, 2014, U.S. Provisional Application 62 / 057,825, filed Sep. 30, 2014, U.S. Provisional Application 62 / 057,820, filed Sep. 30, 2014, U.S. Provisional Application 62 / 044,664, filed Sep. 2, 2014, U.S. Provisional Application 62 / 042,708, filed Aug. 27, 2014, U.S. Provisional Application 62 / 002,709, filed May 23, 2014, U.S. Provisional Application 61 / 979,911, filed Apr. 15, 2014, U.S. Provisional Application 61 / 932,711, filed Jan. 28, 2014, U.S. Provisional Application 61 / 932,704, filed Jan. 28, 2014. U.S. application Ser. No. 15 / 114,762 and PCT / US2...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/496C12N5/00
CPCC12N5/0081A61K31/496A61K31/428A61K31/495A61K31/5377A61P11/00A61P9/10A61P27/02A61K31/404A61K31/4375A61K31/4178A61K31/728A61K9/0048A61K9/0073A61K45/06A61K47/36A61K47/6807A61P25/28C12N15/113C12N2320/30C12N2501/999C12N2503/02C12Q1/485A61K9/0019A61P19/02
Inventor LABERGE, REMI-MARTINCAMPISI, JUDITHDAVALOS, ALBERTDEMARIA, MARCODAVID, NATHANIELVASSEROT, ALAIN PHILIPPEBAKER, DARREN J.CHILDS, BENNETT G.KIRKLAND, JAMES L.TCHKONIA, TAMARVAN DEURSEN, JAN M.A.ELISSEEFF, JENNIFERKIM, CHAEKYUJEON, OKHEEPALMER, ALLYSON K.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com