CMT1A current gene therapy approaches and promising biomarkers

作     者：Marina Stavrou Kleopas AKleopa Marina Stavrou;Kleopas A.Kleopa

作者机构：Neuroscience DepartmentThe Cyprus Institute of Neurology and GeneticsNicosiaCyprus Center for Neuromuscular DisordersThe Cyprus Institute of Neurology and GeneticsNicosiaCyprus 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第7期

页      面：1434-1440页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

主　　题：axonal degeneration biomarkers Charcot-Marie-Tooth disease gene therapy inherited neuropathy mouse models 

摘      要：Charcot-Marie-Tooth neuropathies(CMT)constitute a group of common but highly heterogeneous,non-syndromic genetic disorders affecting predominantly the peripheral nervous system.CMT type 1A(CMT1A)is the most frequent type and accounts for almost~50%of all diagnosed CMT cases.CMT1A results from the duplication of the peripheral myelin protein 22(PMP22)gene.Overexpression of PMP22 protein overloads the protein folding apparatus in Schwann cells and activates the unfolded protein response.This leads to Schwann cell apoptosis,dys-and de-myelination and secondary axonal degeneration,ultimately causing neurological disabilities.During the last decades,several different gene therapies have been developed to treat CMT1A.Almost all of them remain at the pre-clinical stage using CMT1A animal models overexpressing PMP22.The therapeutic goal is to achieve gene silencing,directly or indirectly,thereby reversing the CMT1A genetic mechanism allowing the recovery of myelination and prevention of axonal loss.As promising treatments are rapidly emerging,treatment-responsive and clinically relevant biomarkers are becoming necessary.These biomarkers and sensitive clinical evaluation tools will facilitate the design and successful completion of future clinical trials for CMT1A.