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Treating rotator cuff conditions

a technology for rotator cuffs and conditions, applied in the direction of peptide/protein ingredients, drug compositions, muscular disorders, etc., can solve the problems of pain and shoulder function loss

Pending Publication Date: 2020-12-24
MAYO FOUND FOR MEDICAL EDUCATION & RES
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes methods and materials for treating rotator cuff conditions using BMP-5 polypeptides and inhibitors of SIRT6, SIRT7, or HDAC10 polypeptide expression or activity. These methods and materials can involve injecting a composition containing BMP-5 polypeptides or cells expressing BMP-5 polypeptides into the rotator cuff region of a mammal. The composition can help reduce tendon degeneration, enhance tendon healing, or increase tendon strength. The patent also describes the use of BMP-5 polypeptides and inhibitors of SIRT6, SIRT7, or HDAC10 polypeptide expression or activity in combination with other treatments such as inhibitors of SIRT6 or SIRT7, or cells expressing BMP-5 polypeptides. Overall, the patent provides methods and materials for treating rotator cuff conditions using BMP-5 polypeptides and inhibitors of SIRT6, SIRT7, or HDAC10 polypeptide expression or activity.

Problems solved by technology

A rotator cuff injury can cause pain as well as loss of shoulder function.

Method used

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  • Treating rotator cuff conditions

Examples

Experimental program
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Effect test

example 1

t of Damaged / Ruptured Rotator Cuff Tendons

[0039]High throughput RNA-sequencing of intact and ruptured rotator cuff tendons was performed. The sequencing analysis initially identified the BMP receptor, ACVR1C, as being highly up-regulated in intact tendons versus damaged / ruptured rotator cuff tendons (Table 1).

TABLE 1Expression of BMP receptors in rotator cuff tendon.GeneFold Change Intact vs Diseased TendonACVR13.06ACVR1B4.41ACVR1C52.41ACVR2A4.15ACVR2B2.27ACVRL10.76BMPR1A3.48BMPR1B1.57BMPR22.91

[0040]Once the ACVR1C receptor was identified, the ligands that bind to the ACVR1C receptor as well as downstream signaling molecules related to this receptor were evaluated. An evaluation of sequencing data revealed that BMP5 exhibited the greatest increase in expression amongst the possible ACVR1C receptor ligands, showing an 11.06 fold increase in intact rotator cuff tendon compared to diseased ruptured tendons (Table 2). A decrease in BMP signaling in damaged rotator cuff tendon also was c...

example 2

BMP-5 Polypeptides to Treat Damaged / Ruptured Rotator Cuff Tendons

[0044]BMP-5 polypeptides are synthesized at GMP-grade facilities using eukaryotic cells lines (e.g., CHO cells, HeLa cells, or adipose derived mesenchymal stem cells) to produce BMP-5. The BMP-5 is purified from cell extracts. 0.5 to 10 mg of BMP-5 polypeptide is formulated with 1 to 10 mL of 4 mM HCl or other soluble solution to obtain a liquid composition having a final concentration of about 0.5 to 5 mg / mL. This liquid composition is injected at a dose of 0.1 to 5 mg / mL directly into degenerative or surgically repaired tendons or into the joint space to deliver a total amount of BMP-5 in the range of 0.1 mg and 50 mg per administration.

example 3

Cells Designed to Express BMP-5 Polypeptides to Treat Damaged / Ruptured Rotator Cuff Tendons

[0045]A viral vector or other nucleic acid-based vector designed to express BMP-5 constitutively in a cell is introduced into stem cells or other somatic cell types. These modified cells are formulated with saline or other cell culture medium to obtain a liquid composition having a final concentration of about 100,000 to 20×106 cells / mL. This liquid composition is injected at a dose of about 100,000 to 20×106 cells / mL directly into a damaged tendon or a joint / subacromial space to deliver a total number of cells in the range of 100,000 and 20×106 per administration. BMP-5 expressing stem cells are injected with or without ultrasound guidance. In some cases, these techniques can be used to treat degenerative tendons at risk for rupture or to augment surgical repair of previously ruptured tendons.

Other Embodiments

[0046]It is to be understood that while the invention has been described in conjunct...

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Abstract

This document provides methods and materials related to treating rotator cuff conditions (e.g., rotator cuff tendonitis or rotator cuff injuries such as partial rotator cuff tears). For example, methods and materials for using BMP-5 polypeptides to treat rotator cuff conditions as well as methods and materials for using inhibitors of SIRT6, SIRT7, and / or HDAC10 polypeptide expression or activity to treat rotator cuff conditions are provided.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application is a Continuation of U.S. application Ser. No. 15 / 321,767, filed Dec. 23, 2016, which is a National Stage application under 35 U.S.C. § 371 of International Application No. PCT / US2015 / 039743, having an International Filing Date of Jul. 9, 2015, which claims the benefit of U.S. Provisional Ser. No. 62 / 022,516 filed Jul. 9, 2014. This disclosures of the prior applications are considered part of (and are incorporated by reference in) the disclosure of this application.BACKGROUND1. Technical Field[0002]This document provides methods and materials related to treating rotator cuff conditions (e.g., rotator cuff tendonitis or rotator cuff injuries such as partial or complete rotator cuff tears). For example, this document provides methods and materials for using BMP-5 polypeptides and / or inhibitors of SIRT6, SIRT7, and / or HDAC10 polypeptide expression or activity to treat rotator cuff conditions.2. Background Information[0003]Th...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/18A61K38/17A61P21/00A61K9/00A61K35/28
CPCA61K35/28A61K38/1709A61K9/0019A61P21/00A61K38/1875
Inventor RIESTER, SCOTT M.SPERLING, JOHN W.VAN WIJNEN, ANDRE J.
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
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