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Method to Treat Heart Failure by Reversing Stiffening of Cardiac Muscle Cells

Description:

Brief Description

 

Methods to treat heart failure by interfering and reversing detyrosination of microtubules to restore heart function.

 

Problem

 

Heart failure (HF) is a chronic condition occurring when the heart muscle doesn't pump blood as well as it should, leading to reduced oxygenation of and blood supply to tissues and organs. Current treatments, such as lifestyle changes and medications, are mainly palliative, and there are no effective treatments for ~50% of HF cases.  These untreatable cases are often characterized by an increase in the stiffness of the heart, which impairs its ability to fill with and pump blood.

 

Solution

 

Drs. Prosser and Margulies at the University of Pennsylvania established a causal relationship between reduced contractility of the heart and level of tyrosination of its microtubules. The researchers showed that detyrosination causes stiffening of the heart muscle cells and thus restricts heart contraction. The current invention provides a new method for treating HF aimed at restoring the heart contractile function by either interfering with detyrosination of microtubules or increasing their tyrosination. Therapeutic approaches include small molecules, or gene therapy.

 

 

Advantages

 

•       Addresses the route cause rather than the symptoms of HF

•       First in the class drug for treatment of HF.

 

Applications

 

•       New target to treat heart failure

•       Development of small molecules or gene therapy to treat HF that works by decreasing the stiffness of muscle cells, and thus augmenting heart contractility, by increasing tyrosination of microtubules.

 

Stage of Development

 

•    Proof of concept studies completed in-vitro and ex-vivo on cardiac muscle cells and tissue

•    Proof of function studies on efficacy of treatment performed in-vitro and ex-vivo on cardiomyocytes and cardiac tissue isolated from the diseased heart of human patients

•    Small molecules and gene therapy vectors identified and developed for in-vivo testing

 

Intellectual Property

 

1.       Utility Published in November 2018:  US 20180326022 A1

2.       Provisional patent application pending

 

Reference Media

 

1.       Chen et al., Suppression of detyrosinated microtubules improves cardiomyocyte function in human heart failure, Nat Med. 2018 Aug; 24 (8):1225-1233

2.       Robison et al., Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes. Science. 2016 Apr 22; 352 (6284)

3.       Caporizzo et al., Microtubules provide a viscoelastic resistance to myocyte motion. Biophys J. 2018 Nov 6 ; 115, 1-12

4.       Microtubules’ role in heart cell contraction revealed

 

Desired partnerships

 

• License

• Co-development

 

Docket 17-8222

 


Patent Information:
For Information, Contact:
Viviane Martin
Director, PSOM Licensing Group
University of Pennsylvania
martinv@upenn.edu
Inventors:
Benjamin Prosser
Kenneth Margulies
Keywords: