Copper-ATSM Prevented Motor Neuron Loss, Reduced Brain Inflammation in Mouse Model of SALS, Study Shows

Copper-ATSM Prevented Motor Neuron Loss, Reduced Brain Inflammation in Mouse Model of SALS, Study Shows

Copper-ATSM — a compound originally used as an imaging agent — prevented motor neuron loss and reduced brain inflammation in a mouse model of sporadic amyotrophic lateral sclerosis (ALS), a study showed.

The study, titled “Neuroprotective effect of CuATSM on neurotoxin-induced motor neuron loss in an ALS mouse model,” was published in the journal Neurobiology of Disease.

Originally used as an imaging agent in PET (positron emission tomography) scans, Copper-ATSM — also sometimes written CuATSM — is comprised of a copper atom in complex with ATSM (diacetylbis(N(4)-methylthiosemicarbazonato). In recent years, it has garnered interest from researchers “for its success in extending the lifespan in animals in several neurodegenerative disease models,” the investigators said.

Copper-ATSM, which increases the levels of copper within cells, was previously found to have a therapeutic effect in mouse models of ALS caused by mutations in the gene SOD1. The SOD1 protein uses a copper ion to help it fold correctly. Mutations that alter this folding have been linked to ALS, and were used to generate earlier mouse models of the disease.

It’s believed that regulating copper levels can prevent SOD1 from misfolding, therefore decreasing disease symptoms — but there isn’t much data revealing how the actual mechanism works.

Regardless, researchers say there is pretty solid data that copper-ATSM is beneficial for mice with genetic ALS. But what about ALS that isn’t caused by a known genetic mutation? Sporadic ALS, which has no known cause, accounts for around 90% of all diagnoses.

To find out, the investigators used a model of ALS in which mice were given a neurotoxin called β-sitosterol β-D-glucoside (BSSG) in their food. This induced a slower degeneration process than genetic models, with distinct and progressive features of sporadic ALS.

This model is proposed to be a particularly good representation of Guamian ALS. A high incidence of ALS in Guam has been linked to the consumption of seeds that may harbor neurotoxic compounds.

Some BSSG-fed mice were concurrently treated with copper-ATSM, which was applied to the mice’s skin. These mice performed similarly to control mice — mice that weren’t fed BSSG — on tests of reflexes and motor coordination. Mice that were fed BSSG without additional treatment performed significantly worse.

Additionally, BSSG-fed mice had, on average, 63% fewer motor neurons in their lower spine than control mice. However, when BSSG-fed mice were also treated with copper-ATSM, they had only a 15% decrease in motor neuron numbers compared to controls.

Finally, the mice who were fed BSSG had increased numbers (53% more) of activated microglia — immune cells that are indicative of brain inflammation — in their brains, the study found. Copper-ATSM treatment reduced this total number of cells (41% more). While copper-ATSM-treated mice did have more activated microglia than control mice, they still had fewer than their non-treated counterparts. That suggests that copper-ATSM treatment reduced inflammation in the brains of these mice.

“These outcomes support a broader neuroprotective role for CuATSM beyond mutant SOD models of ALS,” the researchers said.

“It would seem worthwhile pursuing larger and more comprehensive in vivo [in the body] studies to show that CuATSM has unequivocal therapeutic potential in the context of copper homeostasis [equilibrium], in ALS or other neurodegenerative disorders, thereby opening up new avenues for effective treatments,” they concluded.

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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