Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Solna, Sweden.
Department of Neurology, Mayo Clinic, Jacksonville, USA.
Acta Neuropathol Commun. 2020 Dec 7;8(1):217. doi: 10.1186/s40478-020-01093-3.
CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms. CSF1R is predominantly expressed on microglia within the central nervous system (CNS), and thus CSF1R-related leukoencephalopathy is now classified as a CNS primary microgliopathy. This urgent unmet medical need could potentially be addressed by using microglia-based immunotherapies. With the rapid recent progress in the experimental microglial research field, the replacement of an empty microglial niche following microglial depletion through either conditional genetic approaches or pharmacological therapies (CSF1R inhibitors) is being studied. Furthermore, hematopoietic stem cell transplantation offers an emerging means of exchanging dysfunctional microglia with the aim of reducing brain lesions, relieving clinical symptoms and prolonging the life of patients with CSF1R-related leukoencephalopathy. This review article introduces recent advances in microglial biology and CSF1R-related leukoencephalopathy. Potential therapeutic strategies by replacing microglia in order to improve the quality of life of CSF1R-related leukoencephalopathy patients will be presented.
CSF1R 相关脑白质病是一种成人发病的脑白质病，其特征为轴突球体和色素性神经胶质，由集落刺激因子 1 受体（CSF1R）基因突变引起。这种疾病在全球范围内分布，目前尚无治愈方法。CSF1R 相关脑白质病患者的临床表现各不相同，包括认知障碍、进行性神经精神和运动症状。CSF1R 主要在中枢神经系统（CNS）中的小胶质细胞上表达，因此 CSF1R 相关脑白质病现在被归类为 CNS 原发性小胶质细胞病。这种迫切的未满足的医疗需求可能可以通过使用小胶质细胞为基础的免疫疗法来解决。随着实验性小胶质细胞研究领域的快速进展，正在研究通过条件性基因方法或药物治疗（CSF1R 抑制剂）耗尽小胶质细胞后，替代空的小胶质细胞龛位。此外，造血干细胞移植为交换功能失调的小胶质细胞提供了一种新方法，旨在减少脑损伤、缓解临床症状并延长 CSF1R 相关脑白质病患者的生命。本文介绍了小胶质细胞生物学和 CSF1R 相关脑白质病的最新进展。为了提高 CSF1R 相关脑白质病患者的生活质量，我们将介绍通过替代小胶质细胞的潜在治疗策略。
