Vivash Lucy, Malpas Charles B, Meletis Christian, Gollant Meghan, Eratne Dhamidhu, Li Qiao-Xin, McDonald Stuart, O'Brien William T, Brodtmann Amy, Darby David, Kyndt Christopher, Walterfang Mark, Hovens Christopher M, Velakoulis Dennis, O'Brien Terence J
Department of Neurosciences Central Clinical School Monash University Melbourne Australia.
Department of Neurology Alfred Hospital Melbourne Australia.
Alzheimers Dement (N Y). 2022 May 5;8(1):e12299. doi: 10.1002/trc2.12299. eCollection 2022.
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).
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.
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).
Sodium selenate is safe and well tolerated in patients with bvFTD. Randomized-controlled trials are warranted to investigate potential efficacy.
硒酸钠通过激活蛋白磷酸酶2增加tau蛋白去磷酸化。在此，我们报告一项关于硒酸钠作为行为变异型额颞叶痴呆（bvFTD）疾病修饰治疗的开放标签1b期研究。
12名bvFTD参与者接受硒酸钠（15毫克，每日三次）治疗52周。在整个试验过程中进行安全性评估。主要结局为不良事件（AE）、严重不良事件（SAE）的发生频率及停药情况。潜在疗效的次要结局包括认知和行为评估、磁共振成像（MRI）全脑体积，以及脑脊液（CSF）和血液中的总tau蛋白（t-tau）、磷酸化tau蛋白（p-tau）和神经丝轻链（NfL）水平，这些指标在基线和第52周时进行测量。
硒酸钠安全且耐受性良好。所有参与者均完成研究，报告的AE中大多数（64.7%）为轻度。发生了1例SAE，但与治疗无关。在治疗期间，观察到MRI以及认知和行为指标有小幅下降。没有证据表明CSF蛋白水平（t-tau、p-tau或NfL）发生变化。进一步分析显示，在研究过程中测量疾病进展标志物时可分为两个不同的组——一组（n = 4）在12个月的治疗期内脑萎缩明显（减少2.5%至6.5%）且认知和行为下降，另一组（n = 7）认知和行为指标无明显变化且脑萎缩较少（减少0.3%至1.7%）。
硒酸钠在bvFTD患者中安全且耐受性良好。有必要进行随机对照试验以研究其潜在疗效。
