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sodium selenate ftd

Testing a Drug’s Disease-Modifying Potential For Frontotemporal Dementia

By Nicholas Chan | June 14th, 2022

A Phase 2a clinical trial is underway to test the possible benefits of sodium selenate for people living with frontotemporal dementia.

While Alzheimer’s is the leading cause of dementia for older adults, it’s a different story for people under the age of 60: A group of brain disorders all classified together as frontotemporal dementia are the most common type of dementia for people under 60. Out of every 100,000 people, as many as 50 may develop a specific kind of FTD — the behavioral variant, known as bvFTD. As the brain’s frontal lobe deteriorates, people with bvFTD develop symptoms like apathy, disinhibition, lack of judgment and a lack of empathy.

So far, there is no known cure for any form of frontotemporal dementia, the behavioral variant included. But over the past five years or so, a team of researchers have tested a kind of salt for treating neurodegenerative diseases, including bvFTD. Some forms of this salt are used to supplement livestock feed with a source of selenium, or in the manufacturing of glass, or even as an insecticide used to address mealybugs and aphids. But this non-organic compound has also been tested clinically, and now, the second chapter of a human clinical trial for treating the non-genetic behavioral frontotemporal dementia is investigating its potential benefits for patients.

The Phase 2a clinical trial is underway to examine the safety and efficacy of sodium selenate. Researchers believe this compound could have a beneficial impact on bvFTD’s symptoms. Beyond that, they believe, it could actually be able to address the pathology of the disease — and that would be a major milestone.

How could sodium selenate work for frontotemporal dementia’s behavioral variant?

Nearly half of all cases of bvFTD are characterized by the presence of tangles of tau protein in the brain, experts say. According to Dr. Lucy Vivash, an investigator of the trial, tau can become phosphorylated, or “sticky,” in neurodegenerative diseases like bvFTD. But tau, in its normal state, plays a critical role in microtubules, a mechanism that transports chemicals and energy within neurons. As the sticky tau disconnects from the microtubule, neurons’ transport mechanisms begin to break down. These tau proteins could then clump within neurons, compounding the disintegration of these mechanisms. It’s a vicious cycle, Vivash explained.

“When the neuron dies, all of this tau that is within the neuron then gets released into the extracellular space,” Vivash said, “so then the sticky tau can join up with other phosphorylated tau molecules to, again, increase the levels of this sticky tau.” 

This is where sodium selenate could come to play. An enzyme, known as protein phosphatase 2 (PP2A), normally curtails the phosphorylation of tau. But Vivash said both the activity and levels of PP2A are reduced in the neurodegenerative process. 

To reduce tau phosphorylation, sodium selenate steps in. It appears to increase the activity of PP2A, and that could help the brain to clear the abnormal tau through its natural waste management mechanisms, she explained.

Between August 2017 and January 2021, Vivash and her team put sodium selenate to the test in a Phase 1b trial.  In the study, 12 participants with bvFTD, who had a median age of 61, all received sodium selenate over a 52-week period.

Overall, the team reported that sodium selenate was safe and well-tolerated for patients. When it comes to measures of efficacy, all in all, the team reported that patients experienced small declines in brain volume, and in measures of cognitive and behavioral symptoms. After the treatment, there was no overall change in levels of tau, the researchers observed.

But in some patients, there was an increase in tau levels in blood, which Vivash suggests could be an indicator that tau was cleared from their brains. These patients also experienced no changes in cognitive and behavioral symptoms.

Given the small sample size, as well as the lack of randomization and placebo group, Vivash said the team cannot draw any definitive conclusions from the trial data.

To build on the study’s findings, the Phase 2a trial is enrolling 120 patients with bvFTD in Australia and New Zealand, and they will be randomized to a treatment or placebo group for 52 weeks. According to Vivash, people who are interested in enrolling in the study should email selenate@alfred.org.au for more information

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