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Novel and Effective Gene Therapy for Critical Limb Ischemia

Technology Benefits

Clear efficacy in potency assays and in vivo studies Supplying additional potent angiogenic factor, VEGF, which is secreted in a sustained manner from the engineered Mesenchymal stem cells Autologous and allogeneic therapies using engineered mesenchymal stem cell for peripheral artery disease

Technology Application

Treatment for Critical limb ischemiaTreatment of heart tissue of heart attack patients

Detailed Technology Description

Critical limb ischemia (CLI) is characterized by severe obstruction of blood flow to the feet or legs, which results in limb loss if left untreated. It is estimated that 160,000-180,000 major and minor amputations are performed annually in the United States due to CLI. Unfortunately, the limb salvage efforts are often not effective enough to reverse ischemia, despite multiple attempts at revascularization, the wounds still fail to heal. CLI represents a significant unmet medical need since there are currently no effective pharmaceuticals or biologic therapies. Due to their profound effects on blood vessels, vascular endothelial growth factors have received a great deal of attention for promoting therapeutic vascular growth. VEGF delivery via purified protein injections showed potential benefits in Phase I and II clinical trials but did not achieve significance in late phase trials. These effects were hampered by the methods of delivery and the protein has a short life. To generate an improved product VEGF was transduced into human MSCs by a third generation safety modified lentiviral vector. The vector also contains a suicide gene, which provides a safety mechanism allowing cells expressing the suicide gene to be killed if desired administration of a selective agent. The MSC based system is an improved development candidate with clear efficacy in potency assays and in vivo IND-enabling studies, This system offers a definitive strategy of supplying the potent angiogenic factor, VEGF, which is secreted in a sustained manner from the engineered MSC. MSCs migrate into the areas of hypoxic tissue and encourage growth and restructuring of collateral vessels.

Supplementary Information

Patent Number: WO2014036524A2
Application Number: WO2013US57721A
Inventor: NOLTA, Jan | PEPPER, Karen | FIERRO, Fernando | BAUER, Gerhard
Priority Date: 31 Aug 2012
Priority Number: WO2014036524A2
Application Date: 30 Aug 2013
Publication Date: 6 Mar 2014
IPC Current: C12N0015867 | A61K004800
Assignee Applicant: The Regents of the University of California
Title: GENETICALLY MODIFIED MSC AND THERAPEUTIC METHODS | CELLULES SOUCHES MÉSENCHYMATEUSES (MSC) GÉNÉTIQUEMENT MODIFIÉES ET MÉTHODES THÉRAPEUTIQUES
Usefulness: GENETICALLY MODIFIED MSC AND THERAPEUTIC METHODS | CELLULES SOUCHES MÉSENCHYMATEUSES (MSC) GÉNÉTIQUEMENT MODIFIÉES ET MÉTHODES THÉRAPEUTIQUES
Summary: The vector is useful in an isolated cell for: treating peripheral artery disease and/or critical limb ischemia; promoting wound healing; promoting or increasing the rate of angiogenesis or wound healing; decreasing the size of a wound and the time to wound healing; increasing vascularization; and salvaging a limb in a patient with peripheral artery disease or critical limb ischemia, where the vascularization is increased in the ischemic limb (all claimed). Test details are described but no results given.
Novelty: New vector comprising promoters, nucleic acid encoding 165A isoform vascular endothelial growth factor protein, and thymidine kinase gene operatively linked to each other, useful e.g. in isolated cell for treating peripheral artery disease

Industry

Biomedical

Sub Category

Medical Composition

Others

Additional Technologies by these Inventors

• HIV Gene Therapy Treatment

Tech ID/UC Case

23635/2013-059-0

Related Cases

2013-059-0

*Abstract

Critical limb Ischemia (CLI) represents a significant unmet medical need since there are currently no effective pharmaceuticals or biologic therapies for treatment of patients with occluded vessels. Researchers at the University of California, Davis have designed a Mesenchymal Stem/Stromal Cell (MSC) which secretes supraphysiological amounts of human Vascular Endothelial Growth Factor (VEGF) for revascularization of blood vessels and the treatment of peripheral artery diseases such as CLI.

*Principal Investigator

Name: Gerhard Bauer

Department:

Name: Fernando Fierro

Department:

Name: Jan Nolta

Department:

Name: Karen Pepper

Department:

Country/Region

USA