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

Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator

a technology of congestive heart failure and modulator, which is applied in the field of gdf15 modulator, can solve the problems of heart muscle becoming unable to efficiently pump blood around the body, high debilitating and potentially lethal condition, and hospitalization, and achieves the effect of effectively or optimal treatment, reducing or inhibiting the activity of gdf15, and reducing the expression, level or amount of gdf15

Inactive Publication Date: 2017-05-18
AVEO PHARM INC
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention relates to methods and compositions for improving cardiac function in patients with chronic heart failure (CHF) who also have one or more comorbidities, such as cachexia, chronic kidney disease, anemia, iron deficiency, or hypertension. The invention involves administering a GDF15 inhibitor to increase cardiac function in such patients. The invention provides a novel approach for treating CHF by targeting GDF15, a protein that plays a role in the development of CHF. The invention is based on the discovery that inhibiting GDF15 can reduce common comorbidities associated with CHF, such as cachexia, chronic kidney disease, anemia, iron deficiency, or hypertension. The invention includes methods and compositions for using anti-GDF15 antibodies or other GDF15 inhibitors to treat CHF.

Problems solved by technology

Heart failure, also called congestive heart failure, is a common and expensive condition that is highly debilitating and potentially lethal.
It is a leading cause of hospitalization in people aged over 65 years.
When this happens, the heart muscle becomes unable to pump blood efficiently around the body, which can lead to fluid accumulating in the lungs ankles, abdomen and other organs, as well as a feeling of breathlessness.
Hypertrophic cardiomyopathy involves thickening of the heart muscle, which may result in myocardial disarray of the cell structure, stiffening of the heart muscle and high blood pressure.
Reports of the activity of GDF15 in subjects with heart injury have been contradictory and inconclusive.

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
  • Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator
  • Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator
  • Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator

Examples

Experimental program
Comparison scheme
Effect test

example 1

GDF15 Levels in Subjects With and Without Congestive Heart Failure

[0138]Samples of plasma from 245 subjects were examined, and the results are summarized in FIGS. 1-6. GDF15 was assessed at a 1:50 plasma dilution with the DuoSet ELISA Development Kit (R&D Systems, #DY957) according to the manufacturer's recommendation. The inter-assay coefficient of variation (CV) was 5.6%, and the intra-assay CV was 2.9%.

[0139]It was discovered that GDF15 levels were significantly higher in subjects who had been diagnosed with CHF (n=200; mean of about 1900 pg / ml GDF15 for CHF without cachexia; mean of about 3000 pg / ml GDF15 for CHF with cachexia) than in those who were not (n=45; mean of about 1000 pg / ml) (FIG. 1). GDF15 levels were significantly higher in subjects with CHF regardless of whether they presented with cachexia co-morbidity (n=33; mean of about 3000 pg / ml GDF15) or not (n=167; mean of about 1900 pg / ml GDF15) (FIG. 1). Average GDF15 levels increased with increased severity of CHF (FIG....

example 2

Treatment of Cardiac Hypotrophy in an HT-1080 Xenograft Tumor Model

[0144]This Example demonstrates the treatment of cardiac hypotrophy (as indicated by heart weight loss) with an anti-GDF15 antibody 01G06 in an HT-1080 fibrosarcoma xenograft model.

[0145]HT-1080 cells were grown in culture at 37° C. in an atmosphere containing 5% CO2, using Eagle's Minimum Essential Medium (ATCC, Catalog No. 30-2003) containing 10% FBS. Cells were inoculated subcutaneously into the flank of 8-week old female ICR SCID mice with 5×106 cells per mouse in 50% matrigel. Body weight was measured daily. When body weight reached 80%, the mice were randomized into two groups of five mice each. Each group received one of the following treatments: murine IgG control (“mIgG”), or 01G06 dosed at 2 mg / kg on day 1 and day 7, via intra-peritoneal injection. Treatment with antibody 01G06 resulted in body weight increase to initial weight or 100% (p<0.001) (FIG. 7A).

[0146]The data in FIGS. 7A-B indicate that administr...

example 3

In vivo Model of Pressure-Induced Cardiac Hypertrophy

[0150]A reproducible transverse aortic constriction of 65-70% is made in mice, as described in Rockman et al., 1991, PROC. NATL ACAD. SCI., 88:8277-8291. The animals are extubated and allowed to recover, and blood pressure in the left and right carotids is measured. Animals then are dosed with either an anti-GDF15 antibody or control. After seven days, heart size and weight are assessed for the existence and / or extent of cardiac hypertrophy.

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

PropertyMeasurementUnit
Fractionaaaaaaaaaa
Densityaaaaaaaaaa
Densityaaaaaaaaaa
Login to View More

Abstract

The invention provides methods and compositions of treating a subject having a cardiac-related disorder such as congestive or chronic heart failure (CHF), cardiac hypertrophy, cardiac hypotrophy, and other cardiac myopathies / dystrophies. The methods comprise administering an effective amount of a composition that modulates, for example, reduces or inhibits, GDF 15 activity in the subject.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Patent Application No. 62 / 015,093, filed Jun. 20, 2014, incorporated by reference herein in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to methods of using, and compositions containing, a GDF15 modulator for treating a subject having a cardiac disorder or dysfunction, for example, congestive heart failure, chronic heart failure and acute cardiac conditions such as myocardial infarction.BACKGROUND OF THE INVENTION[0003]Heart failure, also called congestive heart failure, is a common and expensive condition that is highly debilitating and potentially lethal. It is a leading cause of hospitalization in people aged over 65 years. Heart failure may be the result of rapid onset, termed “acute heart failure” or may develop over long periods of time, termed “chronic heart failure.”[0004]Heart failure may be associated with a number of other cardiac conditions, disorde...

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
IPC IPC(8): C07K16/22
CPCC07K16/22A61K2039/505C07K2317/76C07K2317/24C07K2317/56C07K2317/565A61P9/04
Inventor GYURIS, JENOLERNER, LORENA
Owner AVEO PHARM INC
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