Columbia University

Technology Ventures

Tissue protection in transplants

Technology #522

“Lead Inventor: Henry N. Ginsberg, M.D.

Transplant protection via Induced Synthesis of Heat Shock Protein HSP 70 :
Organs or cells removed from a donor are susceptible to injury due to the effects of noxious stimuli or stressful conditions such as heat shock (i.e., an abrupt increase in temperature), hypoxia, and ischemia. There is a need to protect ex vivo tissue from these effects in order maintain tissue viability for therapeutic purposes, e.g., transplantation.

Increasing the levels of heat shock protein HSP 70 in a cell to protect transplant organs:
The technology is a novel method for increasing the levels of heat shock protein HSP 70 in a cell. This protein (which comprises the proteins HSP 72 and HSP 73, only the former of which is inducible by heat and other forms of stress) serves as a molecular chaperone that protect proteins from damage due to misfolding or unfolding when a cell is subjected to heat shock. This method relies upon the observation that the aldehydic tripeptide acetyl-leucyl-leucyl-norleucinal (ALLN) both stabilizes HSP 70 levels by inhibiting a protease that normally degrades HSP 70 and dramatically increases synthesis of HSP 70.

Applications:
• Can potentially be used to better preserve an organ ex vivo by protecting it from noxious stimuli or stress.
• Could greatly facilitate organ transplantation.

Advantages:
• Using ALLN to increase HSP 70 levels is a natural way to improve cellular response to injury and/or stressful conditions.

Patent Status: Patent Issued (US 5,942,494) ~ see link below.

Licensing Status: Available for Licensing and Sponsored Research Support

Publications: Evidence That a Rapidly Turning Over Protein, Normally Degraded by Proteasomes, Regulates hsp72 Gene Transcription in HepG2 Cells, M. Zhou et al., Journal of Biological Chemistry, Vol. 271, No. 40, Oct. 1996, pp. 24769-24775.