Ataxin \cite{Becker_2017}
Tamoxifen Treatment in Patients With Motor Neuron Disease: tamoxifen 40 mg daily for one year
Tamoxifen has been reported to decrease TDP-43 aggregates in animal models of ALS via tamoxifen-induced autophagy\cite{Wang_2013}. In a small clinical trial, eighteen ALS patients without mutations in superoxide dismutase-1 (SOD-1) or fused in sarcoma (FUS) gene, were randomized to receive either 40 mg/day tamoxifen or placebo, with all participants receiving riluzole twice daily for a period of 1, 3 or 12 months \cite{Chen_2020}. The primary end-points of time to death or need for mechanical ventilation, was not statistically different between the tamoxifen vs placebo group at any of the time points. However, at a 1, 3 and 6 month evaluation, one of the two secondary end points, ALSFRS-R score, but not forced vital capacity (FVC), decreased less in the tamoxifen group, while there were no statistically significant differences of any end point observed at 12 months. The authors conclude that larger studies would be required to confirm the modest, although transient, improvement in ALSFRS-R scores in the tamoxifen group and whether enhanced autophagy to decrease TDP-43 results in clinical improvement of ALS, particularly if administered at the earliest stages of the disease.
T
DP-43 aggregation was found in more than 90%[9] of patients with sporadic ALS especially who are without mutations in superoxide dismutase-1 (SOD-1) and fused in sarcoma (FUS) genes.[9–12]