ALS is a serious intractable neurological disease in which the muscles of the whole body are atrophied and weakened, and the motor neurons of the whole body disappear as it progresses.The development of treatments that slow the progression is slowly progressing, but there is no curative treatment yet and the cause is unknown.

　However, in ALS, the RNA-binding protein TDP-43 present in the nucleus of the patient's motor neurons disappears, forming abnormal aggregates in the cytoplasm, which cause various adverse events leading to neuronal cell death. Turned out.Therefore, it is attracting attention that the removal of abnormal aggregates of TDP-43 may be directly linked to the curative treatment of ALS.

　This time, the research group has succeeded in developing a new therapeutic antibody that removes abnormal aggregates of TDP-43, the causative protein of ALS.This antibody binds only to abnormal TDP-43 in cultured cells to reduce aggregates, and is highly effective in suppressing cell death caused by aggregates.Fetal mice that produced intracellular antibodies in the brain gave birth and developed normally.Since this antibody is a self-degrading intracellular antibody and is rapidly degraded in cells in which no binding aggregate is present, there is little concern about adverse events due to antibody accumulation, and it is extremely promising as a molecular-targeted therapy.

　In the future, it will be necessary to confirm the effect of ALS model mice that reproduce TDP-43 abnormal aggregates on motor neurons in ALS, and to confirm the safety of primates such as monkeys.It is expected that the unique approach of removing intracellular aggregates using the self-resolution-imparted antibody found this time will open the way for curative treatment of intractable ALS.

Paper information:[Scientific Reports] Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals