A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer’s Disease

Abstract

Treatment with VEL015 at doses up to 30 mg per day for 24 weeks was safe and well-tolerated in patients with AD. Diffusion MR measures appear to be the most sensitive biomarkers to assess disease progression over 24 weeks.

Sodium selenate treatment improves symptoms and seizure susceptibility in a malin‐deficient mouse model of Lafora disease

“…A novel sodium selenate clinical trial has reported to be safe and well tolerated in patients with AD, at doses up to 30 mg per day for 24 weeks. 39 A previous report from Berthier et al and our group 40 showed that administration of certain chemicals ameliorated some neurologic alterations found in our Epm2b À/À malin-deficient mouse model. Thus, both the chaperone 4-phenylbutyric acid (4-PBA) and the neuroprotector metformin produced beneficial effects on the performance of malin-deficient mice in different functional assays.…”

“…No treatment‐related events were observed during sodium selenate administration to malin‐deficient mice, although the gradual decline of the initial improvement in motor and anxiety‐related behavior during treatment may be due to side effects of selenium. A novel sodium selenate clinical trial has reported to be safe and well tolerated in patients with AD, at doses up to 30 mg per day for 24 weeks …”

Treating Alzheimer's disease by targeting iron

“…Dietary selenium is most bioavailable in the organic selenomethionine form; however, a clinical trial of selenomethionine (200 μg·day −1 ) did not reduce dementia incidence in a cohort of healthy, nonselenium‐deficient men over 60 (Kryscio et al, ). Inorganic selenate has been shown to improve cognitive performance in mouse models of tauopathies (Corcoran et al, ; Shultz et al, ; van Eersel et al, ), which prompted a Phase 2, 24‐week double‐blind, placebo controlled, clinical trial of sodium selenate in Alzheimer's patients (Malpas et al, ). Selenate lessened deterioration in brain structures as measured by diffusion tensor MRI, but overall did not impact on cognition in this 24‐week period.…”

Supranutritional Sodium Selenate Supplementation Delivers Selenium to the Central Nervous System: Results from a Randomized Controlled Pilot Trial in Alzheimer's Disease

“…Eligible subjects were ≥ 55 years old; presented with a modified Hachinski score ≤ 4 and a Bmild^to Bmoderate^degree of dementia, as defined by a Mini-Mental Status Examination (MMSE) score of between 14 and 26 at screening; were under treatment with an acetylcholine esterase inhibitor at a stable dose for at least 4 months; and had a documented volumetric MRI brain scan performed within 14 days of baseline that revealed no gross structural abnormality. Exclusion criteria were contraindication for lumbar puncture; history of alcohol and/or other substance abuse; known sensitivity to selenium; presence of any other dementia syndrome or other neurological or psychiatric illness; significant medical disease not adequately controlled; history of epilepsy, diabetes, impaired renal, hepatic, or hematological function; known history of familial AD; current or recent (within 6 weeks of screening) treatment with lithium, NMDA receptor antagonists, steroids, or injectable non-steroidal anti-inflammatory drugs; current treatment with carbamazepine, digoxin, phenobarbitone, phenytoin, or warfarin; and consumption of dietary supplements containing more than 26 μg selenium/day [20].…”

“…It also downregulates the expression of BACE1, a key enzyme involved in the AD-associated amyloid deposition [18], and reduces levels of amyloid and markers of nucleic acid oxidation in APP/PS1 transgenic mice [19]. Our group recently reported results of a Phase IIa exploratory trial of selenate in AD (Vel002) [20], and showed that despite a significant amelioration of brain structural deterioration, there were no significant effects on cognitive performance outcomes. However, it is not proven whether selenate effectively delivers selenium into the central nervous system (CNS).…”