Research Foundation
Kansas State University
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Select Therapeutics against Connexin 46(Cx46) for Treatment of Tumors and other Hypoxic Diseases such as Heart Disease

Reference Number: 08-23

Inventors: Thu Annelise Nguyen; Dolores Takemoto

Background:

Researchers at Kansas State University have discovered that the use of certain commercially available compounds to down-regulate a unique gap junction protein, Connexin 46 (Cx46), could potentially be used to treat certain cancers and other hypoxic diseases such as heart disease.

Cx46 plays an important role in the survival of hypoxic tissues. Hypoxia is a deficiency of oxygen and normal tissues undergo programmed cell death when oxygen reaches low levels. The lens of the eye is the only naturally occurring hypoxic tissue in the human body and the lens is usually the only tissue where Cx46 is found. Drs. Nguyen and Takemoto collaborated to show that breast cancer also expresses Cx46, thus, in general, human tissues which are hypoxic express Cx46. In vitro work showed that when Cx46 is down-regulated with certain commercially available therapeutic compounds, the cells would die at low oxygen levels showing that the targeted down-regulation of Cx46 can be used therapeutically to cause hypoxic tissues such as tumors to die.

In addition, the increase in Cx46 causes a decrease in Cx43, a gap junction protein which is required for normal cell growth and control. Specifically, Cx43 is critical for normal synchronization of cardiac myofibrils. Diseased hearts have a loss of Cx43 due to transient hypoxia. Thus, down-regulation of Cx46 can also be used to treat heart disease.

Advantages:

The invention can potentially be used in the following applications:

• Treatment of tumors
• Treatment of acute or chronic heart disease
• Treatment of retinal ischemia
• Treatment of brain ischemia either transient or during stroke
• Animal health applications

Applications

To best of our knowledge, the intellectual property:

• The first to describe the use of select therapeutics to down-regulate Cx46 for treating hypoxic diseases
• The first to describe an increase in Cx46 during hypoxia drives the loss of Cx43
• Current strategies directed at another protein associated with hypoxia, HIF-1α have shown many side effects as this is broadly found in all cells and is a common gene regulator.
  • The lens is the only hypoxic tissue normally present in healthy individuals and the systemic delivery of select therapeutics will not affect the lens as it is not vascularized tissue.

Technology Readiness

In vitro and in vivo studies have been completed. Mouse in vivo results and in vitro results will be provided upon signing a CDA.

Patent Status

• Provisional patent application filed in June 2008.

Kansas State University Research Foundation seeks to have discussions with companies that are interested in licensing and/or research collaborations.

Interested parties should contact:

National Institute for Strategic Technology Acquisition and Commercialization (NISTAC)
2005 Research Park Circle Manhattan, KS 66502
Tel: 785-532-3900 Fax: 785-532-3909
E-Mail: nistac@ksu.edu