CMT1A current gene therapy approaches and promising biomarkers
Marina Stavrou1
Kleopas A.Kleopa2
1.Neuroscience Department,The Cyprus Institute of Neurology and Genetics,Nicosia,Cyprus2.Neuroscience Department,The Cyprus Institute of Neurology and Genetics,Nicosia,Cyprus;Center for Neuromuscular Disorders,The Cyprus Institute of Neurology and Genetics,Nicosia,Cyprus
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.
机标关键词：currentgeneapproachesbiomarkerspromisingtherapy
论文发表日期：2023-07-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 1434-1440 )
英文信息