Vanderbilt University

Robert D Collins

Jack Jacek Hawiger

Ruth Ann Veach

Jozef Zienkiewicz

Yan Liu

Amy S Major

Danya Liu

Daniel Robinson

Xue Yan Liu

Yao-Zhong Lin

Sheila Downs

Daniel J Moore

Sheila Timmons

The present invention relates to compositions and methods for treating diseases associated with dyslipidemia, including hypercholesterolemia, hypertriglyceridemia, steatohepatitis, atherosclerosis, obesity, hyperglycemia, metabolic syndrome, and related aspects of and conditions associated with metabolic syndrome. The compositions and methods disclosed herein are useful for regulating the lipid balance (lipid homeostasis) in a subject. Compositions and methods including a Nuclear Transport Modifier may be administered to a subject to modulate the transport of transcription factors, mediated by nuclear import adaptors, into the nucleus of a cell resulting in a decrease in cholesterol and triglyceride levels in the blood and liver, a decrease in atherosclerotic lesion size, a decrease in body weight and in hyperglycemia, a reduction of fatty liver inflammation, and an improvement in liver function.

Compositions and methods for treating and preventing hyperlipidemia, fatty liver, atherosclerosis and other disorders associated with metabolic syndrome

Nuclear Transport Modifiers such as cSN50 and cSN50.1, afford in vivo islet protection following a 2-day course of intense treatment in autoimmune diabetes-prone, non-obese diabetic (NOD) mice, a widely used model of Type 1 diabetes (T1D), which resulted in a diabetes-free state for one year without apparent toxicity and the need to use insulin. cSN50 precipitously reduces the accumulation of islet-destructive autoreactive lymphocytes while enhancing activation-induced cell death of T and B lymphocytes derived from NOD mice. cSN50 attenuated pro-inflammatory cytokine and chemokine production in immune cells in this model of human T1D. cSN50 also provides cytoprotection of beta cells, therefore preserving residual insulin-producing capacity. Because intracellular delivery of a Nuclear Transport Modifier peptide such as cSN50 and cSN50.1 can result in lowering of blood glucose levels and may reducing insulin resistance, the compositions, methods and cells described herein can also be used for treating Type 2 diabetes (T2D).

Compositions and methods for preserving insulin-producing cells and insulin production and treating diabetes

The present invention relates to the delivery of biologically active molecules, such as peptides, nucleic acids and therapeutic agents, into the interior of cells by administering to the cells a complex comprising the molecule linked to an importation competent signal peptide. Such delivery can be utilized for purposes such as peptide therapy, gene transfer, and antisense therapy to regulate and/or eradicate systemic inflammatory response syndromes such as endotoxic shock.

Compositions for importing biologically active molecules into cells

The present invention relates to the delivery of biologically active molecules, such as peptides, into the interior of cells by administering to the cells a complex comprising the molecule linked to an importation competent signal peptide. Such delivery can be utilized, for example, to treat and/or prevent inflammatory conditions, e.g., but not limited to, systemic inflammatory reactions such as endotoxic shock, localized inflammatory reactions such as inflammatory skin diseases and conditions, and inflammatory diseases such as autoimmune diseases.

Cell permeable peptides for inhibition of inflammatory reactions and methods of use

Method for importing biologically active molecules into cells

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Nashville, TN, United States of America

Robert D Collins