PMID- 35574563
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220716
IS  - 2352-8737 (Electronic)
IS  - 2352-8737 (Linking)
VI  - 8
IP  - 1
DP  - 2022
TI  - A phase 1b open-label study of sodium selenate as a disease-modifying treatment 
      for possible behavioral variant frontotemporal dementia.
PG  - e12299
LID - 10.1002/trc2.12299 [doi]
LID - e12299
AB  - 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 behavioral 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 behavioral 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 behavioral decline over the 12-month treatment period, and the 
      second group (n = 7) with no detectable change in cognitive and behavioral 
      measures and less brain atrophy (0.3% to 1.7% reduction). CONCLUSION: Sodium 
      selenate is safe and well tolerated in patients with bvFTD. Randomized-controlled 
      trials are warranted to investigate potential efficacy.
CI  - (c) 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease 
      Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's 
      Association.
FAU - Vivash, Lucy
AU  - Vivash L
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
AD  - Department of Neurology Alfred Hospital Melbourne Australia.
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Department of Medicine and Radiology The University of Melbourne Parkville 
      Australia.
FAU - Malpas, Charles B
AU  - Malpas CB
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
AD  - Department of Neurology Alfred Hospital Melbourne Australia.
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Melbourne School of Psychological Sciences The Royal Melbourne Hospital The 
      University of Melbourne Parkville Australia.
FAU - Meletis, Christian
AU  - Meletis C
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Department of Medicine and Radiology The University of Melbourne Parkville 
      Australia.
FAU - Gollant, Meghan
AU  - Gollant M
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
FAU - Eratne, Dhamidhu
AU  - Eratne D
AD  - Neuropsychiatry Royal Melbourne Hospital Parkville Australia.
AD  - Melbourne Neuropsychiatry Centre University of Melbourne and North-Western Mental 
      Health Parkville Australia.
AD  - The National Dementia Diagnostics Laboratory The Florey Institute, The University 
      of Melbourne Parkville Australia.
FAU - Li, Qiao-Xin
AU  - Li QX
AD  - The National Dementia Diagnostics Laboratory The Florey Institute, The University 
      of Melbourne Parkville Australia.
FAU - McDonald, Stuart
AU  - McDonald S
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
AD  - Department of Physiology Anatomy and Microbiology La Trobe University Bundoora 
      Australia.
FAU - O'Brien, William T
AU  - O'Brien WT
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
FAU - Brodtmann, Amy
AU  - Brodtmann A
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Florey Institute of Neuroscience and Mental Health Melbourne.
FAU - Darby, David
AU  - Darby D
AD  - Department of Neurology Alfred Hospital Melbourne Australia.
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Florey Institute of Neuroscience and Mental Health Melbourne.
FAU - Kyndt, Christopher
AU  - Kyndt C
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
FAU - Walterfang, Mark
AU  - Walterfang M
AD  - Neuropsychiatry Royal Melbourne Hospital Parkville Australia.
AD  - Melbourne Neuropsychiatry Centre University of Melbourne and North-Western Mental 
      Health Parkville Australia.
FAU - Hovens, Christopher M
AU  - Hovens CM
AD  - Department of Surgery Royal Melbourne Hospital, University of Melbourne Melbourne 
      Australia.
FAU - Velakoulis, Dennis
AU  - Velakoulis D
AD  - Neuropsychiatry Royal Melbourne Hospital Parkville Australia.
AD  - Melbourne Neuropsychiatry Centre University of Melbourne and North-Western Mental 
      Health Parkville Australia.
FAU - O'Brien, Terence J
AU  - O'Brien TJ
AD  - Department of Neurosciences Central Clinical School Monash University Melbourne 
      Australia.
AD  - Department of Neurology Alfred Hospital Melbourne Australia.
AD  - Department of Neurology Royal Melbourne Hospital Parkville Australia.
AD  - Department of Medicine and Radiology The University of Melbourne Parkville 
      Australia.
LA  - eng
PT  - Journal Article
DEP - 20220505
PL  - United States
TA  - Alzheimers Dement (N Y)
JT  - Alzheimer's & dementia (New York, N. Y.)
JID - 101650118
PMC - PMC9070376
OTO - NOTNLM
OT  - anti-tau treatment
OT  - behavioral variant frontotemporal dementia (bvFTD)
OT  - clinical trial
OT  - fluid biomarkers
OT  - frontotemporal lobar degeneration (FTLD)
OT  - magnetic resonance imaging (MRI)
OT  - phosphorylated tau
OT  - safety and tolerability
OT  - tau
OT  - therapeutic trial
EDAT- 2022/05/17 06:00
MHDA- 2022/05/17 06:01
PMCR- 2022/05/05
CRDT- 2022/05/16 04:44
PHST- 2022/02/09 00:00 [received]
PHST- 2022/03/07 00:00 [revised]
PHST- 2022/03/26 00:00 [accepted]
PHST- 2022/05/16 04:44 [entrez]
PHST- 2022/05/17 06:00 [pubmed]
PHST- 2022/05/17 06:01 [medline]
PHST- 2022/05/05 00:00 [pmc-release]
AID - TRC212299 [pii]
AID - 10.1002/trc2.12299 [doi]
PST - epublish
SO  - Alzheimers Dement (N Y). 2022 May 5;8(1):e12299. doi: 10.1002/trc2.12299. 
      eCollection 2022.