Antisense therapy can slow down Mouse virus disease in mice Antisense therapy can slow down Mouse virus disease in mice

  According to the latest report from JCI Insight, scientists using experimental methods have slowed the progression of scrapie (degeneration of central nervous disease caused by viruses) in experimental mice and greatly extended the lives of rodents. The scientists used antisense oligonucleotides (ASOs), which are synthetic compounds that inhibit the formation of specific proteins.

  When the normal and harmless pr virus protein molecules are abnormal and accumulate in the body clusters and filaments including the brain, viral diseases will occur. People think these diseases are always fatal. Scratching affects sheep and goats and can adapt to rodents. It is closely related to human viral diseases (such as Creutzfeldt-Jakob disease, which is currently incurable). Therefore, scrapie is a valuable experimental model for developing therapies for human viral diseases.

  In the study, scientists from the National Institutes of Health and their colleagues injected ASOs into the spinal fluid of mice that had been infected with scrapie or were attacked by scrapie protein within a few weeks of the injection. Ionis Pharmaceuticals specially designed ASO1 and ASO2 to reduce the supply of normal viral proteins by rodents. Performed at Rocky Mountain Laboratory (RML) in Hamilton, Montana (part of the National Institutes of Health Institute of Allergy and Infectious Diseases) and the Broad Institute in Cambridge, Massachusetts, using different doses of ASO1 and ASO2. Rodent research.

  RML scientists injected mice with ASO1 or ASO2 14 days before infecting mice with scrapie, and then 7 or 15 weeks after infection. Mice treated with ASO1 showed no clinical signs of disease for a median of 250 days, were 82% longer than untreated mice (137 days), and were 81% longer than untreated mice (259 days vs. 143 days) . Mice treated with ASO2 showed no clinical signs of disease in a median time of 272 days, were 99% longer than untreated mice (137 days), and were longer than untreated mice (283 days vs. 143 days). ) Is 98% longer. In the Broad Institute experiment, mice received ASO1 or ASO2 2 weeks before being infected with scrapie, and then received ASO1 or ASO2 7 weeks after infection. Both ASOs delayed weight loss in rodents. The life span of mice treated with ASO1 and ASO2 is longer than that of untreated mice.

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   RML research team also tested ASO against established viral diseases and treated mice 17 weeks after being infected with scrapie (close to the onset of clinical symptoms). Mice treated with ASO1 showed no signs of clinical disease for a median of 189 days, which was 33% longer than untreated mice (142 days). They also showed slower disease progression and 55% longer lifespan than untreated mice (244 days vs. 157 days). ASO2 has no beneficial effects.

  The researchers plan to extend their scrapie ASO research to human viral diseases. Other researchers have seen that human patients with ASO for Alzheimer's disease, amyotrophic lateral sclerosis (Lauger's disease) and Huntington's disease are expected to obtain preliminary results.