Sodium selenate may slow cognitive decline and neurodegenerative damage that is the hallmark of many dementias, including Alzheimer’s Disease, found an Australian clinical trial.
A Monash University-led study has found it a promising reatment for patients with behavioural variant frontotemporal dementia, the second most common form of dementia in under-60s, resulting in a stabilising of what would normally be escalating behavioural issues, and a slowing of brain shrinkage due to the disease. It is the second clinical trial to show that the drug may slow cognitive decline and neurodegenerative damage
The treatment for patients with behavioural variant frontotemporal dementia, the second most common form of dementia in under-60s, resulted in a stabilising of what would normally be escalating behavioural issues, and a slowing of brain shrinkage due to the disease, found a Monash University-led study. It is the second clinical trial to show that the drug, sodium selenate, may slow cognitive decline and neurodegenerative damage
Behavioural variant frontotemporal dementia (bvFTD) is a rapidly progressing destructive disease and can occur in people as young as 35. It is characterised by behavioural disturbances and personality changes and can be highly disruptive and distressing for both patients and their families. Currently there are no treatments or cures for bvFTD and typical survival is five-seven years from diagnosis.
The Phase 1 trial, run in conjunction with the Royal Melbourne Hospital, the only one in Australia targeting non-genetic bvFTD, and one of a handful worldwide, showed that the drug sodium selenate is safe and well-tolerated in patients with bvFTD over a period of 12 months.
Importantly, most of the patients receiving sodium selenate showed no change in their cognitive or behavioural symptoms, and reduced rates of brain atrophy over the trial period. The results from the trial, led by Dr Lucy Vivash from the Monash University's Department of Neuroscience, have just been published in Alzheimer's and Dementia: Translational Research and Clinical Interventions.
In almost half of the cases with bvFTD, the damage to the neurons in the brain is caused by the build-up of a protein called tau. This protein is a major target for research in the prevention and treatment of Alzheimer's and other dementias as a way to reverse the neurodegeneration caused by this tau accumulation.
Vivash said sodium selenate up-regulates an enzyme in the brain that effectively breaks down the tau protein. “We have previously shown, in a Phase 2 trial, that sodium selenate given to patients with mild to moderate Alzheimer’s resulted in less neurodegeneration than in those who did not,” she said.
Importantly, patients in the trial with higher levels of selenium, a breakdown product of sodium selenate, in their bloodstream, showed less cognitive decline.
The research group is now conducting a larger study at many hospitals across Australia and New Zealand to further test whether this drug is beneficial for patients with bvFTD.
Study details
A phase 1b open‐label study of sodium selenate as a disease‐modifying treatment for possible behavioural variant frontotemporal dementia
Lucy Vivash, Charles Malpas, Christian Meletis, Meghan Gollant, Dhamidhu Eratne, Qiao‐Xin Li, Stuart McDonald, William O'Brien, Amy Brodtmann, David Darby, Christopher Kyndt, Mark Walterfang, Christopher Hovens, Dennis Velakoulis, Terence O'Brien.
Published in Alzheimer's & Dementia: Translational Research & Clinical Interventions in 2022
Abstract
Introduction
Sodium selenate increases tau dephosphorylation through protein phosphatase 2 activation. Here we report an open-label Phase 1b study of sodium selenate as a disease-modifying treatment for behavioural variant frontotemporal dementia (bvFTD).
Methods
Twelve participants with bvFTD received sodium selenate (15 mg, three times a day) for 52 weeks. Safety assessments were carried out throughout the trial. Primary outcomes were frequency of adverse events (AEs), serious adverse events (SAEs), and discontinuations. Secondary outcomes of potential efficacy included cognitive and behavioral assessments, magnetic resonance imaging (MRI) whole brain volume, and cerebrospinal fluid (CSF) and blood total tau (t-tau), phosphorylated tau (p-tau), and neurofilament light (NfL) levels, which were measured at baseline and at week 52.
Results
Sodium selenate was safe and well tolerated. All participants completed the study, and the majority (64.7%) of reported AEs were mild. One SAE occurred, which was not treatment related. Small declines in MRI and cognitive and behavioural measures were observed over the treatment period. There was no evidence for change in CSF protein levels (t-tau, p-tau, or NfL). Further analysis showed two distinct groups when measuring disease progression markers over the course of the study—one (n = 4) with substantial brain atrophy (2.5% to 6.5% reduction) and cognitive and behavioural decline over the 12-month treatment period, and the second group (n = 7) with no detectable change in cognitive and behavioural measures and less brain atrophy (0.3% to 1.7% reduction).
Conclusion
Sodium selenate is safe and well tolerated in patients with bvFTD. Randomised-controlled trials are warranted to investigate potential efficacy.
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