Refinement of CCNF gene therapy for MND

The formation of abnormal inclusions of TDP-43 in the cytoplasm of motor neurons is the pathological hallmark of familial and sporadic (non-inherited) MND. The underlying mechanisms that lead to TDP-43 inclusion formation are not known, but cell culture and animal studies demonstrate that cytoplasmic TDP-43 inclusions are toxic to motor neurons. Therefore, therapeutic strategies that clear cytoplasmic TDP-43 are of great interest. It is worth noting that all current biotech company strategies that target TDP-43 do not clear it (as the endogenous pathway for clearance of TDP-43 is unknown), they aim to block its activity by binding it to render it inert (using therapeutic compounds such as antibodies or small molecule inhibitors).