Therapeutics targeting IGFBP7 for the treatment or prevention of heart failure and metabolic diseases
Inventors
Assignees
Publication Number
US-10865412-B2
Publication Date
2020-12-15
Expiration Date
2037-11-03
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Abstract
Insulin-like growth factor-binding protein 7 (IGFBP7) has been identified herein as a therapeutic target for the treatment or prevention of heart diseases, metabolic diseases, and other related disease or conditions. IGFBP7 inhibitors having IGFBP7 expression and/or activity reducing properties are described herein. Treatment methods, and uses, relating to such IGFBP7 inhibitors for the treatment or prevention of heart failure, IGFBP7-related metabolic diseases, and related diseases or conditions are provided.
Core Innovation
The invention identifies insulin-like growth factor-binding protein 7 (IGFBP7) as a therapeutic target for the treatment or prevention of heart failure, metabolic diseases, and related conditions. IGFBP7 inhibitors that reduce IGFBP7 expression and/or activity are described, along with treatment methods and uses relating to such inhibitors for heart failure and IGFBP7-related metabolic diseases.
The problem being solved is heart failure and related metabolic diseases remain major global public health concerns despite extensive efforts. In particular, heart failure with preserved ejection fraction (HFpEF) is increasing and lacks evidence based treatments. The pathophysiology and treatment strategies for HFpEF have been elusive. There is a need for alternative, additional, and/or improved treatments targeting underlying mechanisms.
Claims Coverage
The patent includes multiple independent claims directed to methods of treating heart failure using IGFBP7 inhibitors, alone or in combination with IGF-1 receptor inhibitors, and covers inventive features relating to the nature of the inhibitors and treatment effects.
Method of treating heart failure with IGFBP7 gene silencing nucleic acid inhibitors
A method of treating heart failure by administering an IGFBP7 inhibitor comprising a gene silencing nucleic acid targeting IGFBP7 gene or mRNA to directly reduce IGFBP7 expression or activity in the heart.
Combination therapy with IGFBP7 inhibitor and IGF-1 receptor inhibitor
A method additionally comprising administering an IGF-1 receptor (IGF-1R) inhibitor selected from gene silencing nucleic acids targeting IGF-1R gene or mRNA, anti-IGF-1R antibodies, and/or picropodophyllin to directly inhibit IGF-1R expression or activity in the heart.
Method of treating heart failure with anti-IGFBP7 antibodies
A method of treating heart failure by administering an IGFBP7 inhibitor comprising an anti-IGFBP7 antibody to directly reduce IGFBP7 expression or activity in the heart.
Use of IGFBP7 inhibitors for heart failure comprising HFpEF
The methods cover treatment of pressure overload induced heart failure and heart failure with preserved ejection fraction (HFpEF), attenuating cardiac fibrosis, remodeling, stress-induced cellular senescence, and cardiac hypertrophy.
Human subjects as recipients
The methods include treating human subjects in need thereof.
The claims cover methods of treating heart failure, including HFpEF, via administration of IGFBP7 inhibitors that reduce IGFBP7 expression or activity, optionally in combination with IGF-1 receptor inhibitors, with inhibitors comprising gene silencing nucleic acids or antibodies, focusing on directly reducing target expression or activity in the heart.
Stated Advantages
IGFBP7 targeting provides a new therapeutic strategy for heart failure including HFpEF where effective treatments are lacking.
IGFBP7 inhibition attenuates adverse cardiac remodeling including hypertrophy, fibrosis, and stress-induced cellular senescence.
Targeting IGFBP7 modulates IGF-1 signaling pathways, providing mechanistic intervention in disease processes.
Use of IGFBP7 as a druggable target and as a companion diagnostic allows for personalized medicine approaches.
Documented Applications
Treatment or prevention of heart failure, including pressure overload induced heart failure and heart failure with preserved ejection fraction (HFpEF).
Treatment or prevention of IGFBP7-related metabolic diseases such as diabetes, kidney disease, liver disease, and cardiometabolic dysregulation.},{
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