Developments in the Treatment of Leber Hereditary Optic Neuropathy.
Allotopic expression
Gene therapy
Idebenone
Leber hereditary optic neuropathy
Mitochondrial disease
Optic atrophy
Journal
Current neurology and neuroscience reports
ISSN: 1534-6293
Titre abrégé: Curr Neurol Neurosci Rep
Pays: United States
ID NLM: 100931790
Informations de publication
Date de publication:
12 2022
12 2022
Historique:
accepted:
02
11
2022
pubmed:
23
11
2022
medline:
17
12
2022
entrez:
22
11
2022
Statut:
ppublish
Résumé
To outline the current landscape of treatments for Leber hereditary optic neuropathy (LHON) along the therapeutic delivery pipeline, exploring the mechanisms of action and evidence for these therapeutic approaches. Treatments for LHON can be broadly classified as either mutation-specific or mutation-independent. Mutation-specific therapies aim to correct the underlying mutation through the use of a gene-editing platform or replace the faulty mitochondrial DNA-encoded protein by delivering the wild-type gene using a suitable vector. Recent gene therapy clinical trials assessing the efficacy of allotopically expressed MT-ND4 for the treatment of LHON due to the m.11778G > A mutation in MT-ND4 have shown positive results when treated within 12 months of symptom onset. Mutation-independent therapies can have various downstream targets that aim to improve mitochondrial respiration, reduce mitochondrial stress, inhibit or delay retinal ganglion cell apoptosis, and/or promote retinal ganglion cell survival. Idebenone, a synthetic hydrosoluble analogue of co-enzyme Q
Identifiants
pubmed: 36414808
doi: 10.1007/s11910-022-01246-y
pii: 10.1007/s11910-022-01246-y
pmc: PMC9750907
doi:
Substances chimiques
DNA, Mitochondrial
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
881-892Subventions
Organisme : Medical Research Council
ID : G0701386
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1002570
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR301696
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
Références
Cell. 2015 Apr 23;161(3):459-469
pubmed: 25910206
Lancet Neurol. 2022 Sep 22;:
pubmed: 36155660
Eur J Hum Genet. 2013 Jan;21(1):62-8
pubmed: 22669418
Mitochondrion. 2017 Sep;36:36-42
pubmed: 28093355
PLoS One. 2010 Jul 08;5(7):e11472
pubmed: 20628600
Ophthalmology. 2016 Mar;123(3):558-70
pubmed: 26606867
Science. 1988 Dec 9;242(4884):1427-30
pubmed: 3201231
Ophthalmology. 2018 Jun;125(6):945-947
pubmed: 29426586
J Neuroophthalmol. 2021 Sep 1;41(3):309-315
pubmed: 34415265
Trans Am Ophthalmol Soc. 2007;105:379-91
pubmed: 18427623
Am J Ophthalmol. 2005 Sep;140(3):407-15
pubmed: 16083844
J Neuroophthalmol. 2022 Sep 1;42(3):316-322
pubmed: 35483081
Brain. 2011 Sep;134(Pt 9):e188
pubmed: 21810891
Am J Hum Genet. 2003 Feb;72(2):333-9
pubmed: 12518276
J Neuroophthalmol. 2017 Dec;37(4):371-381
pubmed: 28991104
Nature. 2020 Jul;583(7817):631-637
pubmed: 32641830
Drugs. 2021 Jan;81(1):57-86
pubmed: 33159657
Proc Natl Acad Sci U S A. 2012 May 15;109(20):E1238-47
pubmed: 22523243
Trends Genet. 2018 Feb;34(2):101-110
pubmed: 29179920
Rejuvenation Res. 2007 Jun;10(2):127-44
pubmed: 17518546
Essays Biochem. 2018 Jul 20;62(3):467-481
pubmed: 29980632
Front Neurol. 2021 May 24;12:662838
pubmed: 34108929
Science. 2018 Jan 12;359(6372):
pubmed: 29326244
Brain. 2011 Sep;134(Pt 9):2677-86
pubmed: 21788663
Sci Rep. 2016 Feb 19;6:21587
pubmed: 26892229
Gene Ther. 2022 Jun;29(6):368-378
pubmed: 35383288
Curr Neurol Neurosci Rep. 2020 Apr 15;20(5):11
pubmed: 32296973
Brain. 2022 Nov 09;:
pubmed: 36350566
Med Hypotheses. 2005;65(6):1038-42
pubmed: 16098682
Cell Death Dis. 2018 Sep 26;9(10):1007
pubmed: 30258047
Prog Retin Eye Res. 2011 Mar;30(2):81-114
pubmed: 21112411
Mol Vis. 2012;18:1668-83
pubmed: 22773905
Sci Transl Med. 2020 Dec 9;12(573):
pubmed: 33298565
Ther Innov Regul Sci. 2021 Sep;55(5):1019-1035
pubmed: 34014439
Brain. 2013 Feb;136(Pt 2):e230
pubmed: 23388409
Orphanet J Rare Dis. 2018 Feb 17;13(1):33
pubmed: 29454364
Graefes Arch Clin Exp Ophthalmol. 2019 Dec;257(12):2751-2757
pubmed: 31482278
BioDrugs. 2021 Mar;35(2):201-214
pubmed: 33566264
Am J Ophthalmol. 2022 Sep;241:262-271
pubmed: 35271811
Biochem Int. 1985 Jun;10(6):907-15
pubmed: 2931082
Hum Mol Genet. 2015 Dec 15;24(24):6921-31
pubmed: 26410888
J Neuroophthalmol. 2020 Dec;40(4):547-557
pubmed: 32969847
Biochim Biophys Acta. 2008 Oct;1783(10):1707-17
pubmed: 18513491
Trends Mol Med. 2020 Jul;26(7):698-709
pubmed: 32589937
Can J Ophthalmol. 2013 Oct;48(5):e130-3
pubmed: 24093206
Eye (Lond). 2022 Apr;36(4):818-826
pubmed: 33911213
Mol Ther. 2017 Mar 1;25(3):765-779
pubmed: 28253482
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3693-8
pubmed: 21600768
Biol Rev Camb Philos Soc. 2021 Aug;96(4):1616-1644
pubmed: 33837614
Nat Biotechnol. 2022 Sep;40(9):1378-1387
pubmed: 35379961
Arch Ophthalmol. 2007 Feb;125(2):268-72
pubmed: 17296905
Acta Ophthalmol. 2020 Sep;98(6):e730-e733
pubmed: 32096343
Hum Mol Genet. 2020 Jun 3;29(9):1454-1464
pubmed: 32277753
EMBO J. 1986 Dec 20;5(13):3651-5
pubmed: 2881782
Ophthalmology. 2017 Nov;124(11):1621-1634
pubmed: 28647203
Nat Commun. 2022 Jan 18;13(1):366
pubmed: 35042880
Ann Neurol. 2002 Nov;52(5):534-42
pubmed: 12402249
Arch Neurol. 2012 Mar;69(3):331-8
pubmed: 22410442
J Appl Genet. 2020 May;61(2):195-203
pubmed: 32157656
Am J Hum Genet. 2021 Nov 4;108(11):2159-2170
pubmed: 34670133
Ophthalmology. 2021 May;128(5):649-660
pubmed: 33451738
EBioMedicine. 2016 Aug;10:258-68
pubmed: 27426279
Biochim Biophys Acta. 2012 Feb;1817(2):363-9
pubmed: 22086148
Methods Cell Biol. 2020;155:441-487
pubmed: 32183972
J Neuroophthalmol. 2020 Dec;40(4):558-565
pubmed: 32991388
Ophthalmology. 2020 Aug;127(8):1125-1127
pubmed: 32284191
Sci Adv. 2021 Mar 31;7(14):
pubmed: 33789891