Lexicon Genetics Advances Gene Target for Inflammation and Organ Transplant Rejection
Gene Knockout Prevents Inflammation and Organ Transplant Rejection in Mice
THE WOODLANDS, Texas, Dec. 4 /PRNewswire/ -- Lexicon Genetics Incorporated (Nasdaq: LEXG - news) today announced that the Company has discovered a new role in the immune system for a known enzyme and plans to develop drugs that could be used to block inflammation and potentially even prevent organ transplant rejection. The function of the target, designated LG293, was uncovered through the Company's industrialized gene knockout program in which mice lacking specific genes are studied to uncover favorable medical profiles for developing new drugs. This is the first time that this enzyme has been implicated in regulating the immune system. Scientists at Lexicon are now working to screen for small molecule drugs that act on the enzyme and could eventually be brought into clinical testing for inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, atherosclerosis and systemic lupus erythematosus. The Company anticipates finding molecules that can inhibit LG293 within 12 to 18 months.
Drugs that inhibit the immune system or suppress inflammation contribute to several multi-billion dollar markets. For example, the market for non-steroidal anti-inflammatory agents, drugs such as Cox-2 inhibitors used to treat pain and inflammation associated with rheumatoid arthritis, was $9.5 billion in year 2000 (IMS Health). Included in these markets are therapies that prevent the rejection of organ transplants and treatments for a broad range of inflammatory diseases. Although there are current treatments that offer temporary relief for patients suffering from inflammatory diseases and complications arising from organ transplants, existing therapeutics for many of these diseases and conditions have sub-optimal results with significant side effects.
``We are very excited about the results associated with the latest target disclosed today,'' said Arthur T. Sands, M.D., Ph.D., President and Chief Executive Officer of Lexicon. ``We are demonstrating how our gene knockout technology provides a valuable pipeline of in vivo validated genes and their encoded proteins for the efficient discovery of novel therapeutics.''
The data showed that ``knockout'' mice missing LG293 registered a dramatic reduction in their ability to mount an inflammatory response when challenged. In addition, mice lacking this enzyme were able to accept skin grafts from a completely different strain of mouse without any signs of rejection over a one-month period. Normally, such transplants are rejected within 10 days. LG293 appears to control the deployment of white blood cells that form the ``army'' of the body's immune system. Usually, immune responses protect the body from foreign substances, such as toxins, bacteria and viruses. In some cases, however, these responses are undesirable to the body. Blocking LG293 could provide a significant opportunity to develop new, safer drugs for patients requiring immune system control.
``We find LG293 particularly compelling because we have discovered its profound role and mechanism of action in mammalian physiology,'' said Tamas Oravecz, Ph.D., Lexicon's Director of Immunology. ``We have a strong sense of how a drug which targets this enzyme would control the immune system.''
Lexicon uses a battery of tests conducted in vivo to discover the activity of proteins encoded in the mammalian genome. LG293 is the second target from Lexicon's drug discovery efforts to be unveiled; the Company currently has several additional targets that are rapidly being moved into drug screening in the fields of cardiology, neurology and oncology. Recently, the Company announced its discovery and in vivo validation of a target, designated LG314, for the development of potential treatments for heart disease, obesity and related diseases, such as diabetes... |
