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

US8932559B2 · kind B2 · utility

Assignee

• VANDERBILT UNIVERSITY · US

Inventors

• Jack J. Hawiger · Sharon, US
• Robert D. Collins · Nashville, US
• Daniel J. Moore · Nashville, US
• Jozef Zienkiewicz · Nashville, US
• Ruth Ann Veach · Brentwood, US

Key dates

• Filing date: Oct 5, 2012
• Grant date: Jan 13, 2015
• Expiry date: Oct 5, 2032

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61P37/06
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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).