Method for treating ischemic tissue

An ischemic, tissue technology, applied in gene therapy, chemical instruments and methods, biochemical equipment and methods, etc., can solve the problems of high surgical risk, high recurrence rate of vascular occlusion, and high transplant failure rate

Pending Publication Date: 2020-02-07
UNIV OF MIAMI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, approximately 20% to 40% of patients are not candidates for this intervention due to high procedural risk, high rate of recurrence of vascular occlusion, high rate of graft failure, or unfavorable endovascular anatomy (especially in the sub-knee region)

Method used

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  • Method for treating ischemic tissue
  • Method for treating ischemic tissue
  • Method for treating ischemic tissue

Examples

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example 1

[0086] Impaired blood flow to extremities and soft tissues, usually through large vascular (arterial) and microvascular (capillary) processes, is a major common cause in patients with PAD and CLI. Restoring adequate blood flow to ischemic tissue allows for a successful repair response. Therapeutic angiogenesis refers to the use of drugs, genes, cells, or mechanical devices to induce blood vessel formation in ischemic tissue. The main benefits are inducing the growth of new blood vessels and promoting collateral vessel formation to increase blood flow to ischemic tissues. Angiogenesis may ultimately reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputations, and improve quality of life and prolong survival in patients with CLI, especially those who are not eligible for surgery.

[0087] Adhesion molecules on the cell surface mediate cell-cell interactions and homing. Intercellular interactions mediated by adhesion receptor / ...

example 2

[0099] This example describes the delivery of novel stem cell therapies in the context of the method. In one aspect, administration is derived from BM-engineered tissue repair cells (TRCs) in which E-selectin is pre-installed on the cell surface. These engineered TRCs administered in ischemic limb tissues selectively adhere to activated endothelial cells (ECs) in ischemic tissue vessels expressing elevated counterparts that attract and interact with E-selectin. Ligand) and interact with ECs, especially cells on sprouting tips that reshuffle in sprouting angiogenesis, to promote neovascularization. Alternatively, ECs in wound vessels and tissue cells are primed with E-selectin by using viral vectors to create a supportive tissue microenvironment. E-selectin acts as a docking site for anchoring endogenous or exogenous TRCs expressing E-selectin ligands, thereby increasing the precise interaction / homing of TRCs to ischemic tissue.

[0100] Autologous tissue repair cells (TRC) p...

example 3

[0120] The lack of a reliable animal model of hindlimb gangrene limits molecular studies and preclinical management of critical limb ischemia. This example describes the development and use of a mouse model of hindlimb gangrene to assess the efficacy of gene therapy.

[0121] It was hypothesized that priming of ischemic hindlimb tissue with E-selectin / adeno-associated virus (AAV) would enhance therapeutic angiogenesis and attenuate gangrene.

[0122] Two methods of inducing hindlimb gangrene were tested. In the first approach, FVB mice underwent femoral artery ligation (FAL) to achieve critical limb ischemia. In the second approach, FVB mice were subjected to the FAL combination and administered NG-nitro-L-arginine methyl ester (L-NAME), a nitrogen oxide synthase inhibitor, which further decreased hindlimb perfusion. E-selectin / AAV (treatment) or LacZ / AAV (control) were intramuscularly administered to the hind limbs of gangrene-induced mice before FAL and L-NAME. Gangrene w...

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PUM

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Abstract

The invention provides a method of increasing blood flow or perfusion in an ischemic tissue. The method comprises the steps: inducing angiogenesis, neovascularization or revascularization; increasingskeletal muscle viability; promoting ischemic skin wound healing; treating or preventing gangrene; and / or treating CLI. In various aspects, the method comprises administering to a subject a hybrid adenoassociated virus (AAV) comprising a nucleotide sequence encoding an E-selectin, AAV serotype 2 (AAV2) inverted terminal repeats (ITRs), and a capsid from an AAV other than serotype 2. In various aspects, the method comprises the step of administering to the subject a cell comprising an AAV comprising a nucleotide sequence encoding an E-selectin, AAV2 ITRs, and an AAV2 capsid.

Description

[0001] Grant Funding Disclosure [0002] This invention was made with government support under Grant No. HHSN268201700008C awarded by the National Institutes of Health / National Heart, Lung, and Blood Institute. The government has certain rights in this invention. [0003] Incorporation by Reference of Electronically Submitted Materials [0004] The computer-readable nucleotide / amino acid sequence listing submitted at the same time as this application is incorporated herein by reference in its entirety and identified as follows: 38,503 byte ACII (Text) file named "51600A_SeqListing.txt"; created in 2018 May 1st. technical field [0005] The present disclosure relates to materials and methods for treating ischemic tissue. Background technique [0006] Critical limb ischemia (CLI) is a severe blockage of the arteries supplying the limb and represents an advanced stage of peripheral arterial disease (PAD) caused by systemic atherosclerosis. In atherosclerosis, fatty depos...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/17A61P17/02A61P9/14
CPCA61P17/02A61K48/005C07K14/70564C12N15/86A01K2207/20A01K2227/105A01K2267/0375C12N2750/14143A61K38/178A61K48/0075A61P9/10C12N15/8645A01K67/0275A01K2267/0337A61K35/761
Inventor O·韦拉斯克斯Z-J·刘
Owner UNIV OF MIAMI
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