Researchers hope to make more organs usable for transplantation with new patent

Doctors working at LSU Health Shreveport are continuing to make tremendous advances in therapy in many areas. Most recently, they have made tremendous breakthroughs in drugs for extending transplantation time for liver and kidney and protecting soldiers in combat medicine. In June 2018, U.S. patent #9994585 was awarded to Dr. J. S. Alexander in the Department of Molecular & Cellular Physiology at LSU Health Shreveport, his student, Dr. April Carpenter-Elrod at Ursinus College, and Dr. Trevor Castor with Aphios Corporation for the use of Bryostatin-1, a novel tissue stabilizer in transplantation and trauma surgery. Based on this new patent, Alexander’s group recently submitted a $10 million grant proposal to the Department of Defense to develop Bryostatin-1 as an “ischemia-reperfusion” stabilizer in transplantation and battlefield medicine. The co-investigators on the project are Dr. Felicity Gavins at LSUHS, Dr. Trevor Casto, and Dr. Ari Cohen with Ochsner Health System. This four-year, multi-institutional grant will train surgeons and scientists, and bring new expertise to our medical center. It is one of the first research collaborations between LSU Health Shreveport and Ochsner Health System.

But what is ischemiareperfusion?

When blood flow is temporarily interrupted (known as ischemia), tissues immediately suffer from the lack of oxygen, lack of nutrition and a buildup of waste products. Puzzlingly, a strange thing happens when blood flow is restored (reperfusion): The body’s immune system can “attack” those tissues which were deprived of blood flow, sending in white cells called neutrophils, the most abundant and inflammatory type of white blood cell.

In an ischemia-reperfusion (I/R) injury, this flooding of tissues with white cells causes intense injury by behaving as if a “phantom” infection exists in these tissues. Medical problems from an I/R injury are worse when organs are deprived of blood flow for longer periods, and if the individual suffering this stress is not healthy or if their temperature is higher.

This situation occurs in donor organs and limits their survival, making many transplants tragically fail. This “ischemia reperfusion” also happens often in combat-related trauma and in civilian situations, like motor vehicle accidents or a scenario with major blood loss. When donor organs, such as livers and kidneys, are stored for more than 12 hours or are taken from donor tissues, transplant failure occurs more commonly. This work would make donor organ transport last much longer and remain much more stable over much greater distances. In turn, this would make more organs available than ever before, and make them healthier ones. The approaches being studied now at LSU Health Shreveport for liver (led by Dr. Alexander) and kidney (led by Dr. Gavins) represent powerfully protective drugs, which will change transplant strategies permanently for the better. The methods to limit ischemia-reperfusion are of great interest to the military as well, which may help troops survive injuries that before might have been lethal.

Work with the Aphios Corporation, a long-time collaborator with LSU Health Shreveport, will develop, synthesize and test novel liposome and nanoencapsulated forms of Bryostatin-1, which are the most potent, specific, cost-effective and safest therapeutics of their kind. Ultimately, the success of this project is most excitingly being tested in a Phase 2 human kidney transplant trial run by Dr. Ari Cohen’s group, which will be the first testing of Bryostatin-1 in human transplantation, an extraordinary part of this collaborative team project.

Army researchers have already expressed interest in exploring Bryostatin-1 outside of this proposal with Alexander’s group with the hope to help save American lives and limbs.

For more information on this project, contact Dr. J. Steve Alexander at (318)-675-4151. J. Steven Alexander, Ph.D., is a professor in the Department of Molecular and Cellular Physiology and an adjunct professor in the Department of Neurology at LSU Health Shreveport.