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Digests: NEI News | Mitochondrial Disease News LHON | ARVO Journals LHON | PubMed LHON | Europe PMC LHON | MRC-MBU newsSome reviews of expanding LHON treatment prospects:
In Leber Hereditary Optic Neuropathy— Light at the End of the Tunnel? Asia-Pacific Journal of Ophthalmology Volume 7, Number 4, July/August 2018. Ungsoo Samuel Kim, MD, PhD, Neringa Jurkute, MD, FEBO, and our IFOND board member Patrick Yu-Wai-Man, PhD, FRCOphth, outline modes of Mitochondrial protection, Mitochondrial biogenesis, Gene Therapy, Mitochondrial replacement therapy, and Pluripotent Stem cell therapy. In Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature. Adv Ther. 2018; 35(10): 1510–1518. The authors review the literature and summarize treatment trials.
Is there treatment for Leber Hereditary Optic Neuropathy? Curr Opin Ophthalmol. 2015 Nov; 26(6): 450–457. Jason H. Peragallo, MD and Nancy J. Newman, MD review treatment.
More generally:
Michio Hirano, Valentina Emmanuele, and Catarina M Quinzii. Emerging Therapies for Mitochondrial Diseases. Essays Biochem. 2018 Jul 20; 62(3): 467–481. Published online 2018 Jul 20. doi: 10.1042/EBC20170114 PMCID: PMC6104515 NIHMSID: NIHMS984793 PMID: 29980632 PMC6104515
Valero T. Mitochondrial biogenesis: pharmacological approaches. Curr Pharm Des. 2014;20(35):5507-9. DOI: 10.2174/138161282035140911142118 PMID: 24606795
Carelli V, La Morgia C. Clinical syndromes associated with mtDNA mutations: where we stand after 30 years. Essays Biochem. 2018 Jul 20;62(3):235-254. doi: 10.1042/EBC20170097. Print 2018 Jul 20. PMID: 30030360
And, somewhat against the grain of the narrow drug centred 'silver bullet' paradigm currently dominating medical research and therapy, another call for long overdue research on the safety and efficacy of diet therapy. Maybe a mouse fodder trial is the next step? Maybe survey of insulin resistance in LHON carriers and affected? Since we know Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy, shouldn't we find all avenues to support it? Storoni M, Robert MP, Plant GT. The therapeutic potential of a calorie-restricted ketogenic diet for the management of Leber hereditary optic neuropathy. Nutr Neurosci. 2019 Mar;22(3):156-164. doi: 10.1080/1028415X.2017.1368170. Epub 2017 Oct 10. PMID:28994349 DOI: 10.1080/1028415X.2017.1368170
Some research on the benefits of ketosis on the optic nerve:
Sonia Emperador, Ester López-Gallardo, Carmen Hernández-Ainsa, Mouna Habbane, Julio Montoya, M. Pilar Bayona-Bafaluy & Eduardo Ruiz-Pesini. Orphanet Journal of Rare Diseases volume 14, Article number: 150 (2019). Ketogenic treatment reduces the percentage of a LHON heteroplasmic mutation and increases mtDNA amount of a LHON homoplasmic mutation.
Zarnowski T, Tulidowicz-Bielak M, Zarnowska I, Mitosek-Szewczyk K, Wnorowski A, Jozwiak K, Gasior M, Turski WA. Kynurenic Acid and Neuroprotective Activity of the Ketogenic Diet in the Eye. Curr Med Chem. 2017;24(32):3547-3558. doi: 10.2174/0929867324666170509120257. PMID: 28486923 DOI: 10.2174/0929867324666170509120257
Harun-Or-Rashid M, Pappenhagen N, Palmer P, Smith MA, Gevorgyan V, Wilson GN, Crish SD, Inman DM. Structural and Functional Rescue of Chronic Metabolically Stressed Optic Nerves through Respiration. J Neurosci. 2018 May 30;38(22):5122-5139. doi: 10.1523/JNEUROSCI.3652-17.2018. Epub 2018 May 14. PMID: 29760184 PMCID: PMC5977447 DOI: 10.1523/JNEUROSCI.3652-17.2018
Pflanz NC, Daszkowski AW, James KA, Mihic SJ. Ketone body modulation of ligand-gated ion channels. Neuropharmacology. 2019 Apr;148:21-30. doi: 10.1016/j.neuropharm.2018.12.013. Epub 2018 Dec 15. PMID 30562540 DOI: 10.1016/j.neuropharm.2018.12.013
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