PMID- 34988458
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220429
IS  - 2632-6140 (Electronic)
IS  - 2632-6140 (Linking)
VI  - 3
IP  - 2
DP  - 2021
TI  - Sodium selenate as a disease-modifying treatment for mild-moderate Alzheimer's 
      disease: an open-label extension study.
PG  - e000223
LID - 10.1136/bmjno-2021-000223 [doi]
LID - e000223
AB  - INTRODUCTION: Sodium selenate is a potential disease-modifying treatment for 
      Alzheimer's disease (AD) which reduces hyperphosphorylated tau through activation 
      of the protein phosphatase 2A enzyme. We have shown sodium selenate to be safe 
      and well tolerated in a 24-week, phase 2a double-blind placebo-controlled 
      randomised controlled trial (RCT), also reporting sodium selenate reduced 
      neurodegeneration on diffusion-weighted MRI. This study assessed the safety and 
      tolerability of chronic sodium selenate treatment (up to 23 months) in patients 
      with AD who had been enrolled in the RCT. Cognitive measures served as secondary 
      outcomes of potential disease-modification. METHODS: An open-label extension 
      study of sodium selenate (10 mg three times a day) in patients with AD who had 
      completed the previous RCT. Twenty-eight patients were enrolled. Patients were 
      regularly monitored for safety, adverse events (AEs) and protocol compliance. 
      Cognitive tests were administered for measures of disease progression. RESULTS: 
      Sixteen patients were discontinued by the sponsor, and 12 discontinued for other 
      reasons. Treatment duration ranged from 6 to 23 months. The majority of AEs were 
      mild (83%), and 33% were treatment-related. Common treatment-related AEs were 
      alopecia (21%) and nail disorder (32%), which both resolved either prior to or 
      following cessation of treatment. Two serious AEs occurred, which were not 
      treatment-related. Alzheimer's Disease Assessment Scale-Cognitive Subscale 11 
      score increased 1.8 points over 12 months. DISCUSSION: Chronic sodium selenate 
      treatment is safe and well tolerated in patients with AD. Cognitive measures 
      suggest a slowing of disease progression though this could not be confirmed as 
      the study was not controlled. Further research into sodium selenate as a 
      treatment for AD is warranted.
CI  - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Vivash, Lucy
AU  - Vivash L
AUID- ORCID: 0000-0002-1182-0907
AD  - Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
AD  - Department of Medicine and Radiology, University of Melbourne, Melbourne, 
      Victoria, Australia.
AD  - Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, 
      Australia.
AD  - Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
FAU - Malpas, Charles B
AU  - Malpas CB
AD  - Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
AD  - Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, 
      Australia.
AD  - Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
AD  - Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, 
      Victoria, Australia.
FAU - Hovens, Christopher M
AU  - Hovens CM
AD  - Department of Surgery, University of Melbourne, Melbourne, Victoria, Australia.
FAU - Brodtmann, Amy
AU  - Brodtmann A
AD  - Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, 
      Australia.
AD  - Florey Institute of Neuroscience and Mental Health, University of Melbourne, 
      Melbourne, Victoria, Australia.
AD  - Eastern Cognitive Disorders Clinic, Monash University, Melbourne, Victoria, 
      Australia.
FAU - Collins, Steven
AU  - Collins S
AD  - Department of Medicine and Radiology, University of Melbourne, Melbourne, 
      Victoria, Australia.
FAU - Macfarlane, Stephen
AU  - Macfarlane S
AD  - The Dementia Centre, HammondCare, Melbourne, Victoria, Australia.
FAU - Velakoulis, Dennis
AU  - Velakoulis D
AD  - Neuropsychiatry Unit, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
AD  - Melbourne Neuropsychiatry Centre, University of Melbourne, Melbourne, Victoria, 
      Australia.
FAU - O'Brien, Terence J
AU  - O'Brien TJ
AD  - Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
AD  - Department of Medicine and Radiology, University of Melbourne, Melbourne, 
      Victoria, Australia.
AD  - Department of Neurology, Royal Melbourne Hospital, Parkville, Victoria, 
      Australia.
AD  - Department of Neurology, Alfred Hospital, Melbourne, Victoria, Australia.
LA  - eng
PT  - Journal Article
DEP - 20211216
PL  - England
TA  - BMJ Neurol Open
JT  - BMJ neurology open
JID - 101775450
PMC - PMC8679123
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - cognition
COIS- Competing interests: The authors report the following disclosures outside of this 
      study: LV reports personal fees from Biogen Australia and research funding from 
      Biogen, LMI and Eisai. CMH reports issued patents US 9,415,063 and US 8,920,951. 
      TJOB reports research funding from Biogen, Eisai, UCB, Anavex and Praxis. CM, AB, 
      SC, SM and DV have nothing to disclose.
EDAT- 2022/01/07 06:00
MHDA- 2022/01/07 06:01
PMCR- 2021/12/16
CRDT- 2022/01/06 06:04
PHST- 2021/09/20 00:00 [received]
PHST- 2021/11/22 00:00 [accepted]
PHST- 2022/01/06 06:04 [entrez]
PHST- 2022/01/07 06:00 [pubmed]
PHST- 2022/01/07 06:01 [medline]
PHST- 2021/12/16 00:00 [pmc-release]
AID - bmjno-2021-000223 [pii]
AID - 10.1136/bmjno-2021-000223 [doi]
PST - epublish
SO  - BMJ Neurol Open. 2021 Dec 16;3(2):e000223. doi: 10.1136/bmjno-2021-000223. 
      eCollection 2021.