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脊髓性肌萎缩症患者的蛋白质生物标志物特征。

Protein biomarker signature in patients with spinal and bulbar muscular atrophy.

机构信息

Nido Biosciences, Inc., Boston, Massachusetts, USA.

University College London (UCL), London, United Kingdom.

出版信息

JCI Insight. 2024 May 30;9(13):e176383. doi: 10.1172/jci.insight.176383.

DOI:10.1172/jci.insight.176383
PMID:38973610
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11383357/
Abstract

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressing disease with limited sensitive biomarkers that support clinical research. We analyzed plasma and serum samples from patients with SBMA and matched healthy controls in multiple cohorts, identifying 40 highly reproducible SBMA-associated proteins out of nearly 3,000 measured. These proteins were robustly enriched in gene sets of skeletal muscle expression and processes related to mitochondria and calcium signaling. Many proteins outperformed currently used clinical laboratory tests (e.g., creatine kinase [CK]) in distinguishing patients from controls and in their correlations with clinical and functional traits in patients. Two of the 40 proteins, Ectodysplasin A2 receptor (EDA2R) and Repulsive guidance molecule A (RGMA), were found to be associated with decreased survival and body weight in a mouse model of SBMA. In summary, we identified what we believe to be a robust and novel set of fluid protein biomarkers in SBMA that are linked with relevant disease features in patients and in a mouse model of disease. Changes in these SBMA-associated proteins could be used as an early predictor of treatment effects in clinical trials.

摘要

脊髓延髓肌肉萎缩症（SBMA）是一种进展缓慢的疾病，其敏感的生物标志物有限，难以支持临床研究。我们分析了来自 SBMA 患者和匹配的健康对照者的多个队列的血浆和血清样本，在近 3000 个测量的蛋白中鉴定出 40 个高度可重现的 SBMA 相关蛋白。这些蛋白在与骨骼肌表达和与线粒体及钙信号转导相关的过程相关的基因集内丰富。许多蛋白在区分患者和对照者方面优于当前使用的临床实验室检测（例如肌酸激酶[CK]），且与患者的临床和功能特征具有相关性。这 40 个蛋白中的 2 个，外胚层发育不良蛋白 A2 受体（EDA2R）和排斥性导向分子 A（RGMA），在 SBMA 的小鼠模型中发现与存活时间和体重降低相关。总之，我们鉴定出了 SBMA 中一组我们认为是稳健且新颖的体液蛋白生物标志物，与患者和疾病小鼠模型中的相关疾病特征相关。这些 SBMA 相关蛋白的变化可用作临床试验中治疗效果的早期预测指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/e25bc2046e2b/jciinsight-9-176383-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/83b82527c9ab/jciinsight-9-176383-g081.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/b9025713a714/jciinsight-9-176383-g082.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/64fc2e4277c4/jciinsight-9-176383-g083.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/2c3a337b9ba9/jciinsight-9-176383-g084.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/e21f72978817/jciinsight-9-176383-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/e25bc2046e2b/jciinsight-9-176383-g086.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/83b82527c9ab/jciinsight-9-176383-g081.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/b9025713a714/jciinsight-9-176383-g082.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/64fc2e4277c4/jciinsight-9-176383-g083.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/2c3a337b9ba9/jciinsight-9-176383-g084.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/e21f72978817/jciinsight-9-176383-g085.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99c7/11383357/e25bc2046e2b/jciinsight-9-176383-g086.jpg

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