Thioredoxin: a novel mucolytic agent for the treatment of cystic fibrosis

Tech ID: 1996-07

Summary

National Jewish Health researchers have been investigating the effects of reducing agents such as thiols in disease.  Initial studies demonstrated the ability of of one di-thiol, thioredoxin (Trx) to induce production of manganese superoxide dismutase (MnSOD), which protects cells against oxidant injury.  Further investigation has shown that Trx, a low molecular protein, is also a powerful mucolytic agent with therapeutic potential for cystic fibrosis.

Potential Applications

Oxidant lung injuries in premature infants and patients on respirators; Lung diseases involving mucous production, like Cystic Fibrosis; Asthma; Cancer; Mustard Gas exposure

Advantages of Invention

Thioredoxin is a naturally occurring compound that can be found in the extracellular space.  It is also highly soluble and can be delivered at relevant concentrations.  Trx delivers a mucolytic effect similar to DNAse, but with much less subsequent elastase activity increase.

State of Development

Our scientists have shown that:

  • Thioredoxin decreases the viscosity of cystic fibrosis sputum
  • Thioredoxin inhibits elastase activity

In rats, reduced recombinant human

  • thioredoxin instilled intratracheally increases neutrophils and cytokines, but not when CF sputum is present

Further R&D Required

Test compound in mouse model of CF to confirm non-inflammatory effects in vivo

Patent

Issued US Patents #7,534,438, 5,985,261 and 7,195,766. Other US and international patents pending.

Publication

Rancourt, et al. 2007 Free Radic Biol Med. 42(9):1441-53 .

Lee, et al. 2005 Am J Physiol Lung Cell Mol Physiol. 289(5):L875-82.

Rancourt, et al. 2004 Am J Physiol Lung Cell MolPhysiol. 286(5):L931-8

Das, et al. 1997  Am J Respir Cell Mol Biol.17(6):713-26.

Inventors

Carl White, MD, Rees Lee, MD and Kumuda Das, PhD

Licensing Status - This technology is available for licensing

 

For Further Information, Contact:
Emmanuel Hilaire, PhD
Manager
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: (303) 398-1262
Fax: (303) 270-2352
HilaireE@njhealth.org

Appointments

1-800-222-5864

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