Experimental drugs can effectively prevent rejection of mice heart transplants

According to a new study by scientists at Weill Cornell Medicine and Brigham and Women's Hospital through recombinant human proteins, experimental drugs that block the activation of immune cell components effectively prevent rejection of mice heart transplants.

The findings published in the Proceedings of the National Academy of Sciences on December 12 describe a compound developed by medical researchers at Weill Cornell. The inhibits the cellular structure known as the immune proteasome while avoiding constitutive proteasomes. Proteasomes help cells to break down regulatory proteins to regulate their behavior. The constitutive proteasome is present in all cells, while the immunoproteasome is expressed predominantly in the cells of the immune system.

The currently-approved proteasome inhibitors also target two types of proteasomes. They are used in transplantation medicine to block immune cell function and reduce graft rejection. However, proteasome inhibitors in all cells of the body can cause toxicity in transplanted organs and hosts. The researchers demonstrated that their compound DPLG3, a highly selective and reversible inhibitor of the immune proteasome, only shuts down the immune proteasome, leaving the constitutive proteasome. DPLG3 reduces the number of immune cells in the graft. Inhibitors also increase the expression of "exhaustive markers" on the remaining immune cells. Exhaustive markers are typical of immune cells, reducing the ability to attack foreign cells. These changes protect the organ from rejection, while protecting the body from toxic side effects of non-selective proteasome inhibitors, such as bone marrow and nervous system damage.

"Transplant patients often have to take long-term toxic, broad-spectrum immunosuppressive agents, which increases the risk of infection, cancer and toxicity of the graft itself," said Dr. Carl Nathan, director of Department of Microbiology and Immunology and RA Rees Pritchet, professor of microbiology, and Cornell's professor of medical microbiology and immunology and medicine, "Selective blocking of the immune proteasome without affecting the constitutive proteasomes in other host cells and transplant organ cells can help patients to receive grafts on a long-term basis and improve organ transplants."

Medical researchers of Weill Cornell led by Dr. Gang Lin, associate professor of microbiology and immunology, co-author of the study, designed DPLG3, which is highly selective for the immune proteasome and is highly selective for long-term exposure. Dr. Nathan and Dr. Lin are co-inventors of the DPLG3 and have submitted patents. Flarebio offers good quality recombinant proteins such as recombinant PIGR at competitive prices.