Patent ID: 8865411
Filing Date: 2014-10-21
Classification: A61K,A61P,C12N

Abstract:
1. A method of inhibiting TDP-43 mediated cellular toxicity, the method comprising contacting a cell comprising a genetic construct for expressing a toxicity inducing amount of a C-terminal variant of TDP-43 consisting of amino acids 188 to 414 of SEQ ID NO: 1, with an effective amount of an agent that inhibits expression or activity of at least one gene selected from the group consisting of DBR1, PCL6, SAK1, YCK2, MEC1, UBP7, RGA2, KEL1, DIP5, ROM2, VHS1, YHR131C, SLF1, HRP1, PBP1, KEM1, MSN5, SRO9, SFG1, MSA1, PIB2, SLG1, MTH1, CDC6, TSC11, SOL1, KIN3, PBP2, SET3, CCE1, SIW14, YDR067C, DOM34, MGD1, RPL16, and human homologs thereof, or an agent that increases expression or activity of at least one gene selected from the group consisting of FMP48, VTS1, XRS2, HSP104, TIS11, BFR1, ICS2, YKL171W, PGM1, ADY3, RIM15, CYC8, RDR1, TIF4631, MRPL39, FLD1, MSN2, PBL16B, NHX1 and human homologs thereof, wherein when said gene is to be inhibited said agent is an antisense, ribozyme or siRNA complementary to mRNA transcribed from said gene such that it binds said mRNA under physiological conditions, and inhibits its translation and wherein when said expression of said gene is to be increased, a vector encoding a polypeptide encoded by said gene is introduced into said cell.