CuATSM, also known as copper (II) diacetylbis(N4-methylthiosemicarbazone), is a chemical compound that has been studied for its potential therapeutic effects in patients with amyotrophic lateral sclerosis (ALS).
SOD1, a protein involved in 2% of ALS cases contains a binuclear Cu/Zn site in each subunit. So it seems there is some relation between copper and ALS. It is believed that CuATSM's mechanism of action involves restoring the balance of copper ions and preventing the buildup of toxic forms of copper. But this is at best highly speculative.
CuATSM is one of those drugs highly promoted on social networks as an effective treatment for SOD1-ALS, yet the evidence was unclear. There were several pre-clinical studies that were very encouraging ... by the same team.
There were clinical studies. On January 7th, 2019, television spots and a media release stated that CuATSM slowed disease progression by 70%! in the phase 1 clinical trial participants. This resulted in an international outcry for people with ALS/MND to access CuATSM. The Phase 2/3 trial was completed in late 2021 although the outcome of the clinical trial has yet to be announced.
Up to 80 patients were planned to be treated with CuATSM or placebo for 24 weeks. The studied drug is administered orally, once a day before breakfast.
The present study set out to perform a comparative analysis of Amyotrophic Lateral Sclerosis pathology.
- In 6 ALS patients that had been administered CuATSM and riluzole (4 X ALS-TDP and 2 X ALS-SOD1)
- In 6 ALS patients that had been administered riluzole only ( (4 X ALS-TDP and 2 X ALS-SOD1) ).
The authors' results revealed no significant difference in neuron density or TDP-43 burden in the motor cortex and spinal cord of patients that had received CuATSM compared to patients that had not.
In patients that had received CuATSM, immunoreactive astrocytes were observed in the motor cortex and reduced Iba1 density (Iba1/ AIF-1 is usually found in macrophages and microglia) in the spinal cord.
However, no significant difference in measures of astrocytic activity and SOD1 immunoreactivity was found with CuATSM treatment.
These findings, in this first postmortem investigation of patients with Amyotrophic Lateral Sclerosis in CuATSM trials, demonstrate that in contrast to that seen in preclinical models of disease, CuATSM does not significantly alleviate neuronal pathology or astrogliosis in patients with Amyotrophic Lateral Sclerosis.