South Alabama Medical Science Foundation

Other

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

Isis Pharmaceuticals, Inc.

Richard Eric Honkanen

Nicholas M Dean

James M Downey

Brandon Marshall D'Arcy

Mark Raymond Swingle

Compositions, methods, and systems for modifying sterol metabolism in a subject is disclosed. In some embodiments, the subjects may be administered one or more mammalian cells modified to express at least one sterol degrading enzyme derived from a bacterium. In many embodiments, the cell is a macrophage or monocyte stably expressing three or more enzymes that aid in opening the &#x3b2; ring of cholesterol. The disclosed compositions and methods may be useful in lowering cholesterol levels in a subject in need thereof. In some embodiments, the subject may have a genetic predisposition to atherosclerosis.

Compostions and methods for enabling cholesterol catabolism in human cells

The invention provides a method of increasing expression of p21in cells to decrease proliferation of the cells, the method comprising decreasing levels of PP5 protein in the cells. The invention further provides a method of treating or preventing an abnormal condition resulting from a defect in a tumor suppressor gene in a subject that results in decreased induction of p21in the cells of the subject, the method comprising administering to the subject an amount of a compound effective to decrease levels of PP5 protein in the cells of the subject.

Decreasing cell proliferation by decreasing levels of PP5

Oligonucleotides are provided which are targeted to nucleic acids encoding human serine/threonine protein phosphatases and which are capable of inhibiting protein phosphatase expression. Methods of inhibiting the expression of human protein serine/threonine phosphatases using oligonucleotides of the invention are also provided. The present invention further comprises methods of preventing or inhibiting hyperproliferation of cells and methods of treating abnormal conditions, including cancer, using oligonucleotides of the invention.

Antisense oligonucleotide inhibition of human serine/threonine protein phosphatase gene expression

The invention provides a method of increasing expression of p21 in cells to decrease proliferation of the cells, the method comprising decreasing levels of PP5 protein in the cells. The invention further provides a method of treating or preventing an abnormal condition resulting from a defect in a tumor suppressor gene in a subject that results in decreased induction of p21 in the cells of the subject, the method comprising administering to the subject an amount of a compound effective to decrease levels of PP5 protein in the cells of the subject.

A composition comprises a glucocorticoid receptor agonist and a compound which decreases levels of active human serine/threonine protein phosphatase 5 protein in cells. The glucocorticoid receptor agonist is dexamethasone and the compound is an antisense oligonucleotide of about 8 to 50 nucleotides in length which is targeted to a nucleic acid encoding human serine/threonine protein phosphatase 5. The composition is useful in a method of enhancing glucocorticoid activity, and in a method of enhancing the inhibition of hyperproliferation of cells where the inhibition is by contacting the cells with a compound which decreases levels of active human serine/threonine protein phosphatase 5 protein in cells. The compound is thus useful to enhance glucocorticoid therapy and to enhance inhibition of hyperproliferation relating to PP5.

Glucocorticoid receptor agonist and decreased PP5

Antisense oligonucleotides to human serine/threonine protein phosphatase

Fostriecin and a compounds structurally related to fostriecin diminish myocardial infarction and delay the onset of cell injury in an ischemic heart. There is a strong correlation between myocardial protection and the inhibition of certain serine/threonine protein phosphatases. The present invention is drawn to a method for administering fostriecin as a pharmacological compound to reduce the size of a myocardial infarction. Further, administration of fostriecin is useful also as an adjunct therapy to treatment with thrombolytic agents or angioplasty to limit the size of infarction. The most advantageous feature of the method of the present invention is that administration of fostriecin diminishes infarct volume and cell injury even when added after ischemia conditions occurred. In addition to the use of the method of the present invention for limiting damage due to myocardial infarction, the method of the present invention can be employed to delay damage associated with tissue storage for organ transplantation.

Growing community of inventors

Mobile, AL, United States of America

Richard Eric Honkanen