Translational Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Bristol, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Canynge Hall, Bristol, BS8 2PR, UK.
Nat Commun. 2022 Aug 9;13(1):4655. doi: 10.1038/s41467-022-31450-w.
Friedreich's ataxia (FA) is an inherited progressive neurodegenerative disease for which there is no proven disease-modifying treatment. Here we perform an open-label, pilot study of recombinant human granulocyte-colony stimulating factor (G-CSF) administration in seven people with FA (EudraCT: 2017-003084-34); each participant receiving a single course of G-CSF (Lenograstim; 1.28 million units per kg per day for 5 days). The primary outcome is peripheral blood mononuclear cell frataxin levels over a 19-day period. The secondary outcomes include safety, haematopoietic stem cell (HSC) mobilisation, antioxidant levels and mitochondrial enzyme activity. The trial meets pre-specified endpoints. We show that administration of G-CSF to people with FA is safe. Mobilisation of HSCs in response to G-CSF is comparable to that of healthy individuals. Notably, sustained increases in cellular frataxin concentrations and raised PGC-1α and Nrf2 expression are detected. Our findings show potential for G-CSF therapy to have a clinical impact in people with FA.
弗里德赖希共济失调（FA）是一种遗传性进行性神经退行性疾病，目前尚无经过证实的可改变疾病进程的治疗方法。在此，我们对 7 名 FA 患者进行了一项开放性标签、试验性研究，对其施用重组人粒细胞集落刺激因子（G-CSF）（EudraCT：2017-003084-34）；每位患者接受一个疗程的 G-CSF（培非格司亭；每天每公斤 128 万单位，连续 5 天）。主要终点是 19 天内外周血单个核细胞中 frataxin 水平的变化。次要终点包括安全性、造血干细胞（HSC）动员、抗氧化剂水平和线粒体酶活性。试验达到了预设的终点。我们发现，FA 患者施用 G-CSF 是安全的。G-CSF 诱导的 HSC 动员与健康个体相当。值得注意的是，细胞内 frataxin 浓度的持续增加以及 PGC-1α 和 Nrf2 表达的升高被检测到。我们的研究结果表明，G-CSF 疗法有可能对 FA 患者产生临床影响。
