Peripheral Neuropathy Group, Department of Molecular Genetics, Flanders Interuniversity Institute for Biotechnology, Institute Born Bunge, University of Antwerp, Antwerp, Belgium.
Ann Neurol. 2013 Sep;74(3):391-6. doi: 10.1002/ana.23987.
Charcot-Marie-Tooth (CMT) neuropathies are inherited neuromuscular disorders caused by a length-dependent neurodegeneration of peripheral nerves. More than 900 mutations in 60 different genes are causative of the neuropathy. Despite significant progress in therapeutic strategies, the disease remains incurable. The increasing number of genes linked to the disease, and their considerable clinical and genetic heterogeneity render the development of these strategies particularly challenging. In this context, cellular and animals models provide powerful tools. Efficient motor and sensory tests have been developed to assess the behavioral phenotype in transgenic animal models (rodent and fly). When these models reproduce a phenotype comparable to CMT, they allow therapeutic approaches and the discovery of modifiers and biomarkers. In this review, we describe the most convincing transgenic rodent and fly models of CMT and how they can lead to clinical trial. We also discuss the challenges that the research, the clinic, and the pharmaceutical industry will face in developing efficient and accessible treatment for CMT patients.
腓骨肌萎缩症（CMT）是一种遗传性周围神经疾病，由周围神经的长度依赖性神经退行性变引起。超过 60 个不同基因中的 900 多个突变可导致这种神经病变。尽管在治疗策略方面取得了重大进展，但该疾病仍然无法治愈。越来越多的疾病相关基因及其显著的临床和遗传异质性使得这些策略的开发极具挑战性。在这种情况下，细胞和动物模型提供了强大的工具。高效的运动和感觉测试已被开发出来，用于评估转基因动物模型（啮齿动物和果蝇）的行为表型。当这些模型产生类似于 CMT 的表型时，它们允许进行治疗方法和修饰因子以及生物标志物的发现。在这篇综述中，我们描述了最令人信服的 CMT 转基因啮齿动物和果蝇模型，以及它们如何能够转化为临床试验。我们还讨论了研究、临床和制药行业在为 CMT 患者开发有效和可及的治疗方法方面将面临的挑战。
