Gendron Tania F, Daughrity Lillian M, Heckman Michael G, Diehl Nancy N, Wuu Joanne, Miller Timothy M, Pastor Pau, Trojanowski John Q, Grossman Murray, Berry James D, Hu William T, Ratti Antonia, Benatar Michael, Silani Vincenzo, Glass Jonathan D, Floeter Mary Kay, Jeromin Andreas, Boylan Kevin B, Petrucelli Leonard
Department of Neuroscience, Mayo Clinic, Jacksonville, FL.
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Jacksonville, FL.
Ann Neurol. 2017 Jul;82(1):139-146. doi: 10.1002/ana.24980.
As potential treatments for C9ORF72-associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139-146.
随着用于治疗与C9ORF72相关的肌萎缩侧索硬化症（c9ALS）的潜在疗法进入临床试验阶段，确定c9ALS的预后生物标志物成为当务之急。我们发现，脑脊液（CSF）中磷酸化神经丝重链（pNFH）的水平可预测c9ALS患者的疾病状态和生存期，并且在一段时间内基本稳定。此外，与没有C9ORF72基因扩增的肌萎缩侧索硬化症（ALS）患者相比，c9ALS患者的pNFH水平更高，疾病进展更快，发病后的生存期更短。这些数据支持将脑脊液pNFH用作临床试验的预后生物标志物，这将增加成功开发c9ALS治疗方法的可能性。《神经病学纪事》2017年；82:139 - 146。
