Evaluation of triumeq treatment on a TDP-43 mouse model of amyotrophic Lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the accumulation of TAR DNA Binding Protein (43 kDa; TDP-43) within the cytoplasm of neurons. Endogenous retroviruses (ERVs) have been implicated in ALS pathology and the application of antiretroviral therapy, specifically Triumeq, has been proposed for treatment of ALS. However, evidence to support the actions of Triumeq in ALS is lacking. This study investigates the effects of the antiretroviral treatment Triumeq on ALS disease that occurs through TDP-43 pathology by utilising the doxycycline (Dox)-suppressible rNLS8 TDP-43 expression mouse model. In this model, TDP-43 accumulation in the cytoplasm is induced after removal of Dox. Disease was assessed through measures of body weight, neurological score, motor function, urinary p75^ECD and inflammatory marker expression. Mice were treated with Triumeq and TDP-43 pathology and inflammatory marker expression examined. Triumeq treatment significantly improved motor function early on in the disease course but did not impact other disease progression markers or disease endpoint. In this TDP-43 ALS mouse model, there was a positive association of TDP-43 mRNA levels with transcription factor ATF4, and inflammatory markers CXCL10 and IRF-1, and Triumeq treatment negated this association. Triumeq treatment transiently and modestly improved motor function and influenced TDP-43 associated inflammatory gene expression in an ALS mouse model. These findings support the potential use of Triumeq in treating TDP-43-associated ALS and supports further investigation to better understand if the beneficial actions of Triumeq are via disruption of TDP-43-driven inflammation in ALS.