However, perrin said, sod1 g93a mice used

Lock key molecular path that the body uses to enhance the immune response was found to delay onset and prolong survival of mice with a disease that mimics human, say scientists supported MDA

in Cambridge, Mass. ALS TDI Researchers say they have discovered that the immune system way in the end they were locked in overactive SOD1 mice (mice with the familial form of BAS through the SOD1 gene mutation) and was also hyperactive in 56 percent (35 of 63) of blood samples taken from people with ALS, most of whom have no family ALS. "This is a relationship between mouse and human data have played an important role in addressing the Institute to continue development of this molecule as a potential treatment of bass," said Steve Perrin, General Director of the Institute, Senior Scientist, who coordinated the study. This discovery opens up new and promising directions for the treatment of BAS, expanding understanding of the mechanisms of this disease, and ALS TDI checks methods designed to identify these mechanisms and treatments that aim them. About ALS mechanisms About 1 to 3 percent of BAS caused by any of a large number of mutations in the chromosome-21, known as gene SOD1. Mice with a mutation of the SOD1 G93A is called a general model for the study of human disease and were used in experiments, ALS TDI. In mice used lasix without a prescription in experiments was rapidly progressive, severe ALS-like disease. There is increasing evidence that the failure of the immune system, at least part of the disease ALS. ALS TDI and other researchers found abnormal immune system activity in animal models of disease, and ALS TDI researchers have observed it in ALS patients blood samples. On new results supported MDA ALS TDI group published their findings online March 28, 2010 in Nature Genetics. The team used a strategy called "full analysis transkriptoma" which involves looking at the activity levels of all genes in the body during illness or other specific conditions. Finding that certain genes related to immune response was abnormally active in the SOD1 G93A mouse studies, scientists have conducted more research and decided to try to block the interaction of two molecules involved in the immune response: CD40 and CD40 ligand. When the body mounts immune response to protein, it considers threatening - "antigen" - specialized antigen-presenting cells display antigen immune T cells. When they do, antigen-presenting cell docking sites ("receptors") type known as CD40, dealing respectively with fittings - CD40 ligand - on the surface of T cells. These two parts - CD40 receptor and CD40 ligand - fit together like a key to lock, signaling that the immune system is a full-scale attack is necessary. Blocking this interaction was found to be useful in animal models of transplantation of tissues, where the purpose is to make animals suffer another animal cells and in animal models of autoimmune disease in which the goal is to make animals suffer for its own cells, which he mistakenly attacks. ALS TDI researchers decided to use the blocking protein (antibody) to CD40 ligand and CD40 terminate participation CD40 receptor ligand. These antibodies have dubbed ALSTDI-00846. They treated 44 mice with antibody, and 45 were "empty" injection for comparison. Compared with the control group, the mice lost weight much slower pace. In addition, anti-CD40 ligand treatment with a significant delay in the beginning of paralysis (eight days) compared with the beginning of the paralysis in the control group. And, antibodies of mice receiving survived an average of nine days longer than untreated animals were also significant. For comparison, ALS TDI researchers found that ALS mice are given riluzola (only for the treatment of BAS approved the U.S. Food and Drug Administration) survive only an average of three days longer than untreated mice. Unfortunately, when researchers tried to start treatment CD40 ligand antibody in day 80, after the appearance of overt symptoms of ALS in mice, they saw no therapeutic effect on the onset or progression and no extension of survival. The need for treatment in early disease process, preferably before symptoms appear, can be problematic for people, because most of ALS is not diagnosed until the disease is already developing for some time. However, Perrin said, SOD1 G93A mice used in these experiments is very difficult, quickly progressing form of the disease, and it is not clear that such early treatment is absolutely necessary, most people with this disease. Role of MDA MDA, with its promise Quest Ogi, began to support ALS TDI in 2007, making $ 18 million grant from the Institute for 2007-2009 and awarded an additional $ 2. 5000000 in 2010. ALS patient blood samples used in these experiments were collected in several MDA / ALS centers. Values ​​for people with ALS This study adds to the already ample evidence that part of the immune system behave correctly in ALS. Research continues to show that blocking the interaction between the immune system molecules can significantly slow down the disease ALS, at least in mice. In addition, initial action of the immune system is out of the spinal cord and brain (CNS) and, therefore, can get medical treatment without violating the central nervous system barriers. Therapies that require a central nervous system is much more difficult in the development and administration. Ligand CD40 antibodies can be developed for use in human ALS, say researchers, and this may be one of many possible strategies to modulate the immune system. These antibodies are being studied for their potential to treat various diseases in which the hyperactive immune system plays an important role, such as rheumatoid arthritis and lupus. "Human blood work we have done can be used to identify groups of patients for clinical trials that would be likely to respond to CD40 ligand antibodies," said Perrin. "Now we have a set of potential biological markers of disease that can be used by the pharmaceutical industry partners to advance research quickly."