Mitochondrial DNA maintenance defects: potential therapeutic strategies

被引：11

作者：

Almannai, Mohammed ^{[1
]}

El-Hattab, Ayman W. ^{[2
]}

Azamian, Mahshid S. ^{[3
]}

Ali, May ^{[3
]}

Scaglia, Fernando ^{[3
,4
,5
]}

机构：

[1] King Abdul Aziz Med City, King Abdullah Specialized Childrens Hosp KASCH, Genet & Precis Med Dept GPM, Minist Natl Guard Hlth Affairs MNG HA, Riyadh, Saudi Arabia

[2] Univ Sharjah, Coll Med, Dept Clin Sci, Sharjah, U Arab Emirates

[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[4] Texas Childrens Hosp, Houston, TX USA

[5] Prince Wales Hosp, Joint BCM CUHK Ctr Med Genet, Shatin, Hong Kong, Peoples R China

来源：

MOLECULAR GENETICS AND METABOLISM | 2022年 / 137卷 / 1-2期

关键词：

Mitochondria; mtDNA replication; mtDNA depletion; Preclinical studies; Nucleoside bypass therapy; Clinical trials; HEMATOPOIETIC GENE-THERAPY; IN-VITRO SUPPLEMENTATION; THYMIDINE KINASE; NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY; POLYMERASE-GAMMA; MURINE MODEL; LIVER-TRANSPLANTATION; MTDNA LEVELS; DEPLETION; MUTATIONS;

D O I：

10.1016/j.ymgme.2022.07.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Mitochondrial DNA (mtDNA) replication depends on the mitochondrial import of hundreds of nuclear encoded proteins that control the mitochondrial genome maintenance and integrity. Defects in these processes result in an expanding group of disorders called mtDNA maintenance defects that are characterized by mtDNA depletion and/or multiple mtDNA deletions with variable phenotypic manifestations. As it applies for mitochondrial disor-ders in general, current treatment options for mtDNA maintenance defects are limited. Lately, with the develop-ment of model organisms, improved understanding of the pathophysiology of these disorders, and a better knowledge of their natural history, the number of preclinical studies and existing and planned clinical trials has been increasing. In this review, we discuss recent preclinical studies and current and future clinical trials con-cerning potential therapeutic options for the different mtDNA maintenance defects.(c) 2022 Elsevier Inc. All rights reserved.

引用

页码：40 / 48

页数：9

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