Case Number 114064 - Inducing Liver Regeneration by Administering Hepatocyte-derived Exosomes

Contact: Jill Uhl
Phone: 513-558-5621

Description:  Dr. Alex Lentsch has made the unexpected discovery that hepatocyte-derived exosomes, that contain neutral ceramidase and sphingosine kinase, promote hepatocyte proliferation and liver regeneration after partial liver hepatectomy (i.e. liver resection) or ischemia/reperfusion (I/R) injury. I/R injury is regarded as one of the most important contributors to liver graft dysfunction. The results obtained suggest that hepatocyte-derived exosomes may be a therapeutic application for liver resection surgery and transplantation success.

Liver resection surgeries are most often indicated for patients with liver tumors. Up to 75% of the liver tissue may be removed, but this volume is often limited by other functional diseases such as cirrhosis which is a co-morbidity for 80% of liver cancer patients in the USA leaving only 10-20% of patients as candidates for surgery. For those that qualify the surgery can provide good results with the liver regenerating its preoperative size in about 6-8 weeks.

In the USA about 17,000 adults and children who have been medically approved for liver transplants are on a waiting list for donated livers to become available. Each year more than 1,500 people die while waiting for a donated liver to become available. About 6,000 liver transplants are performed annually. Given this transplant organ shortage it is critically important to preserve the integrity of each transplanted liver graft.

The success rate of liver transplantation is illustrated by the approximately 86% one-year and 78% three-year survival rate. Unfortunately complications do arise following even the most exacting liver transplant procedure. After liver transplantation the incidence of biliary complications varies from 10-30%. These biliary complications lead to an increase of graft dysfunction and patient morbidity and in some cases even to graft loss and retransplantation. The complications are associated with an increased mortality rate of 8-15%. Liver I/R injury following liver transplantation causes up to 10% of early transplant failures and can lead to acute and chronic rejection. Ischemic-type biliary lesions (IBTLs) which underlie liver transplant failures have an incidence of 10-15% following liver transplantation.

It is the hope of this new technology to be further developed into a standard protocol therapy during liver transplantation as well as liver surgery. It is the hope of this new technology to be further developed into a standard protocol therapy during liver transplantation as well as liver surgery. It is thought that when successful FDA clinical trials are completed that the invention could offer advantages such as: • Significant improvement in organ recovery after major liver surgery • Allowing use of marginal liver tissue in transplantation increasing the pool of transplantable livers • Permitting use of more radical resection of liver tissue in surgery to treat cancer

The global market for regenerative medicine was $16.4 billion in 2013 and was growing at a CAGR of 23.2%. The market portion associated with liver regeneration may be up to $1 billion. This suggests that the current invention might realize over $100 million in market potential.

US Provisional Patent Application No. 61/984,295 filed April 25, 2014 (Compositions and Methods for Inducing Liver Regeneration by Administering Hepatocyte-derived Exosomes)