Myocardial Therapeutics, Inc.

Medstar Health Research Institute, Inc.

The United States of America As Represented by the Department of Health

Georgetown University

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Medstar Research Institute, Inc.

Fuchs, Shmuel

Epstein, Stephen E.

Leon, Martin B.

Kornowski, Ran

Stephen E Epstein

Ran Kornowski

Mary Susan Burnett

Shmuel Fuchs

Anton Wellstein

Toren Finkel

Ellis F Unger

Ronald G Crystal

Martin B Leon

Steven M Pincus

Lorne F Erdile

Stephan Zbinden

Marcel O Schmidt

Juanhui Zhu

Raul G Guzman

Edith Speir

Yi Fu Zhou

Jianhui Zhu

Amir Najafi

Edith H Speir

Described herein are conditioned medium and processed conditioned medium, each of which comprises secreted stem cell factors; compositions containing conditioned medium and/or processed conditioned medium and a delivery polymer. The conditioned medium, processed conditioned medium and compositions may be used to promote blood vessel growth and healing of injured tissues.

Conditioned medium obtained from stem cells and its use in therapy

Described herein are homing polypeptides that home to atherosclerotic plaque(s) in mammals and nucleic acids that encode such polypeptides. Also described are methods for detecting and treating conditions or disorders associated with, or characterized, by elevated levels of homing polypeptides that home to atherosclerotic plaque and/or vulnerable plaque.

Polynucleotides that home to atherosclerotic plaque

Described herein are polypeptides that home to developing microvasculature, (also referred to as developing microvessels), such as newly developing microvasculature in mammals, particularly in humans, and to DNA that encodes such polypeptides. These polypeptides are referred to herein as developing microvasculature homing polypeptides. In a specific embodiment, the homing peptides are collateral vessel endothelia (CVE) homing polypeptides, which have been shown to home to collateral vessel endothelia after ischemia.

Genes and proteins that home to developing microvessels

An individual's risk profile for developing a cardiovascular disorder or for experiencing a cardiovascular event is determined by 1) measuring levels of certain stress-evoked proteins including heat shock proteins (HSPs), cytokines, adhesion molecules, chemokines, and the like, or titers of the antibodies targeted to them, or 2) determining the number of seropositive responses to a group of pathogens that have been associated with the presence of atherosclerosis and/or clinical events related to atherosclerosis. The measured levels are compared with clinically derived standards that define the association of these markers with cardiovascular disease. These markers are independent of traditionally recognized risk factors.

Method of using physiological markers to estimate cardiovascular risk

A method of treating cardiac or myocardial conditions comprises the administration of an effective amount of autologous bone marrow. The bone marrow may optionally be stimulated and/or administered in combination with a pharmaceutical drug, protein, gene or other factor or therapy that may enhance bone marrow production of angiogenic growth factors and/or promote endothelial cell proliferation or migration or blood vessel formation.

Intramyocardial injection of autologous bone marrow

A flexible tissue injection catheter is used to accomplish injections at a precisely controlled depth of precisely controlled volumes of a therapeutic or diagnostic agent into an interior body cavity, such as the epicardium or myocardium of the heart. In one embodiment, the invention method includes repeated injections at spaced intervals along the myocardium or epicardium of sterile fluid containing autologous bone marrow aspirate to promote angiogenesis. For myocardial injection, depth penetration is controlled by using a catheter that allows the operator to control depth penetration by means of an adjustable needle stop attached to the catheter handle. In another embodiment depth penetration during epicardial injections is controlled by use of an injection catheter having an operator-controlled adjustable needle stop that produces a sensible signal, such as a visible or audible signal, marking each increment of needle tip exposed by operation of the adjustable needle stop.

Methods for controlled depth injections into interior body cavities

The present invention provides a method of selectively expressing DNA in neointimal cells in an injured blood vessel of a subject comprising administering a replication-deficient recombinant adenovirus which functionally encodes the DNA to the blood vessel at the site of injury, such that the adenovirus remains at the site of injury for a time sufficient for the adenovirus to selectively infect neointimal cells and thereby selectively express the DNA in neointimal cells. In particular, the invention provides administering a replication-deficient recombinant adenovirus which functionally encodes a DNA encoding a protein or an antisense ribonucleic acid. This method can be used to treat restenosis and, relatedly, prevent neointimal cell proliferation.

Efficient and selective adenoviral-mediated gene transfer into vascular neointima

Methods for aspiration and filtering of a bodily fluid containing undesired components are provided and for treatment of the bodily fluids in a sterile environment in preparation for reinjection of treated aspirate into a donor subject. The invention methods are particularly designed to facilitate transfection of aspirated cells with angiogenesis promoting molecules without danger to the technician or the donor prior to reinjection of the treated cells, either percutaneously or via a surgical opening via a catheter or injection needle. A pressure actuator attached to the sterile container is used to express treated fluids in precisely controlled volumes. The invention methods include delivery of treated fluids using a hand-held device with audible cues that correspond to an operator-selected injection volume and/or audible cues that correspond to needle penetration depth selected by the operator.

Methods for sterile aspiration/reinjection of bodily fluid

Disclosed and claimed are compositions and methods for therapy and/or prevention of restenosis and/or atherosclerosis. The compositions can include an agent for decreasing viral load of cytomegalovirus, such as an immunological composition or vaccine against cytomegalovirus (CMV) containing at least one epitope of interest of CMV and/or an expression system which expresses at least one epitope of interest of CMV. Such compositions can include at least one epitope of p53. Alternatively, the compositions can include at least one epitope of p53 and/or an expression system which expresses the epitope. The methods can include administering the compositions to a patient in need of such therapy and/or prevention. Additionally, compositions and methods for diagnosing atherosclerosis and/or restenosis, or susceptibility thereto, including screening a sample from a patient for antibodies to CMV and/or CMV proteins and/or screening a sample from a patient for specific viral proteins that predict whether the virus has been reactivated and/or antibodies thereto and/or detecting whether CMV nucleic acid, e.g., mRNA is present in peripheral blood monocytes (PBMCs) and/or detecting a cellular-mediated immune response to CMV peptides or proteins is present and/or HLA phenotyping and/or HLA genotyping. Embodiements can include a skin test.

Restenosis/atherosclerosis diagnosis, prophylaxis and therapy

The present invention provides a method of inhibiting restenosis of a blood vessel in a mammal after mechanical treatment of the vessel to reduce a stenosis. The method includes contacting proliferating smooth muscle cells in the vessel with an antisense oligonucleotide directed against a cellular division cycle gene product. This gene product can be one of the following: c-myc, PCNA, and cyclin B.sub.1. The antisense oligonucleotide is used in an amount effective to inhibit translation of the cellular division cycle gene product in the cell.

Inhibition of cell proliferation using antisense oligonucleotides

A method for facilitating in a damaged heart or a heart in need of improved circulation the growth of cardiac blood vessels while reducing the risk of undesired vascularization in other areas of the body comprises:

Growing community of inventors

Rockville, MD, United States of America

Stephen E Epstein