Case Number 115038 - Manipulation of the acid sphingomyelinase and ceramide pathways to improve the quality of stored packed red blood cells

Contact: Jill Uhl
Phone: 513-558-5621

Description:  Dr. Tim Pritts’ laboratory has discovered an additive to improve the quality of stored packed red blood cells and which will prevent a series of biochemical and physical changes known as the red blood cell storage lesion that take place as red blood cells age.

Problem: Blood transfusion is the only alternative for treatment of anemia and requires storage of packed red blood cell (pRBC) units. However, pRBC degrades with time during storage, developing a condition known as red blood cell storage lesion. The lesion is harmful to transfusion recipients and is associated with greater risk of infection, organ failure and death. Thus, there is an imperative to improve the quality of stored pRBC units to lessen the degree of harm to transfusion recipients.

Solution: The present invention provides an additive (amitriptyline, a common antidepressant) to be supplied at the time of storage that reduces red blood cell storage lesion by altering the sphingolipid content of the cell membrane. Specifically, it causes a decrease in activity of the enzyme acid sphingomyelinase and a decrease in accumulation of ceramide. These changes result in decreased hemolysis of erythrocytes, decreased formation of microparticles, decreased phosphatidylserine expression and increased preservation of cellular structure. Mice transfused with amitriptyline-treated pRBC’s show decreased lung injury compared to pRBC units treated with vehicle, as measured by preservation of normal lung architecture, decreased leukocyte infiltration, preservation of tight junction proteins and decreased cytokine production. It is expected that treatment of pRBC with amitriptyline would reduce harm experienced by human recipients of blood transfusions.

Advantages: Manipulation of the sphingolipid system via decreasing acid sphingomyelinase and ceramide has the potential to improve the quality of stored pRBC and could possibly extend its shelf life.

The target market for the invention is the blood devices and consumables market. Red blood cell transfusion is a critical and life-saving treatment for severe anemia caused by disease or chemotherapy, or by blood loss due to trauma or major surgery. After collected, red blood cells have a shelf life of 42 days, and hospitals must stock a variety of blood types and try not to run out of any category. In the U.S. alone, a total of 30 million blood components are transfused each year, with the average red blood cell transfusion consisting of approximately 3 pints. The global blood devices and consumables market was valued at $27.27 billion in 2012 and is expected to grow to $49.16 billion by 2019. Stored pRBC would make up a portion of the total market. It is possible that the stored pRBC portion of the global market is worth at least $1.0 billion

A provisional patent application (62/147,748) has been filed on this technology