Mitochondrial DNA maintenance defects: potential therapeutic strategies

doi:10.1016/j.ymgme.2022.07.003

Review

. 2022 Sep-Oct;137(1-2):40-48.

doi: 10.1016/j.ymgme.2022.07.003. Epub 2022 Jul 6.

Mitochondrial DNA maintenance defects: potential therapeutic strategies

Mohammed Almannai¹, Ayman W El-Hattab², Mahshid S Azamian³, May Ali³, Fernando Scaglia⁴

Affiliations

¹ Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.
² Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, Shatin, Hong Kong. Electronic address: fscaglia@bcm.edu.

PMID: 35914366
PMCID: PMC10401187
DOI: 10.1016/j.ymgme.2022.07.003

Review

Mitochondrial DNA maintenance defects: potential therapeutic strategies

Mohammed Almannai et al. Mol Genet Metab. 2022 Sep-Oct.

. 2022 Sep-Oct;137(1-2):40-48.

doi: 10.1016/j.ymgme.2022.07.003. Epub 2022 Jul 6.

Authors

Mohammed Almannai¹, Ayman W El-Hattab², Mahshid S Azamian³, May Ali³, Fernando Scaglia⁴

Affiliations

¹ Genetics and Precision Medicine Department (GPM), King Abdullah Specialized Children's Hospital (KASCH), King Abdulaziz Medical City, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia.
² Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
³ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁴ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Texas Children's Hospital, Houston, TX, USA; Joint BCM-CUHK Center of Medical Genetics, Prince of Wales Hospital, Shatin, Hong Kong. Electronic address: fscaglia@bcm.edu.

PMID: 35914366
PMCID: PMC10401187
DOI: 10.1016/j.ymgme.2022.07.003

Abstract

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 disorders in general, current treatment options for mtDNA maintenance defects are limited. Lately, with the development 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 concerning potential therapeutic options for the different mtDNA maintenance defects.

Keywords: Clinical trials; Mitochondria; Nucleoside bypass therapy; Preclinical studies; mtDNA depletion; mtDNA replication.

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References

1. El-Hattab AW, Craigen WJ, Scaglia F, Mitochondrial DNA maintenance defects, Biochim. Biophys. Acta Mol. basis Dis 1863 (6) (2017) 1539–1555, 10.1016/j.bbadis.2017.02.017. - DOI - PubMed
1. Taanman JW, The mitochondrial genome: structure, transcription, translation and replication, Biochim. Biophys. Acta 1410 (2) (1999) 103–123, 10.1016/s0005-2728(98)00161-3. - DOI - PubMed
1. Viscomi C, Zeviani M, MtDNA-maintenance defects: syndromes and genes, J. Inherit. Metab. Dis 40 (4) (2017) 587–599, 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed
1. Almannai M, El-Hattab AW, Scaglia F, Mitochondrial DNA replication: clinical syndromes, Essays Biochem. 62 (3) (2018) 297–308, 10.1042/EBC20170101. - DOI - PubMed
1. Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F, Clinical trials in mitochondrial disorders, an update, Mol. Genet. Metab 131 (1) (2020) 1–13, 10.1016/j.ymgme.2020.10.002. - DOI - PMC - PubMed

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[1] El-Hattab AW, Craigen WJ, Scaglia F, Mitochondrial DNA maintenance defects, Biochim. Biophys. Acta Mol. basis Dis 1863 (6) (2017) 1539–1555, 10.1016/j.bbadis.2017.02.017. - DOI - PubMed

[2] El-Hattab AW, Craigen WJ, Scaglia F, Mitochondrial DNA maintenance defects, Biochim. Biophys. Acta Mol. basis Dis 1863 (6) (2017) 1539–1555, 10.1016/j.bbadis.2017.02.017. - DOI - PubMed

[3] Taanman JW, The mitochondrial genome: structure, transcription, translation and replication, Biochim. Biophys. Acta 1410 (2) (1999) 103–123, 10.1016/s0005-2728(98)00161-3. - DOI - PubMed

[4] Taanman JW, The mitochondrial genome: structure, transcription, translation and replication, Biochim. Biophys. Acta 1410 (2) (1999) 103–123, 10.1016/s0005-2728(98)00161-3. - DOI - PubMed

[5] Viscomi C, Zeviani M, MtDNA-maintenance defects: syndromes and genes, J. Inherit. Metab. Dis 40 (4) (2017) 587–599, 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed

[6] Viscomi C, Zeviani M, MtDNA-maintenance defects: syndromes and genes, J. Inherit. Metab. Dis 40 (4) (2017) 587–599, 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed

[7] Almannai M, El-Hattab AW, Scaglia F, Mitochondrial DNA replication: clinical syndromes, Essays Biochem. 62 (3) (2018) 297–308, 10.1042/EBC20170101. - DOI - PubMed

[8] Almannai M, El-Hattab AW, Scaglia F, Mitochondrial DNA replication: clinical syndromes, Essays Biochem. 62 (3) (2018) 297–308, 10.1042/EBC20170101. - DOI - PubMed

[9] Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F, Clinical trials in mitochondrial disorders, an update, Mol. Genet. Metab 131 (1) (2020) 1–13, 10.1016/j.ymgme.2020.10.002. - DOI - PMC - PubMed

[10] Almannai M, El-Hattab AW, Ali M, Soler-Alfonso C, Scaglia F, Clinical trials in mitochondrial disorders, an update, Mol. Genet. Metab 131 (1) (2020) 1–13, 10.1016/j.ymgme.2020.10.002. - DOI - PMC - PubMed

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Mitochondrial DNA maintenance defects: potential therapeutic strategies

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Mitochondrial DNA maintenance defects: potential therapeutic strategies

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