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NMN extended lifespan of mice with a mitochondria disorder called Leigh syndrome

nmn

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#1 Phoebus

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Posted 06 March 2019 - 03:10 PM


 

Article OPEN Published: 

28 February 2019

 

Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease

Scientific Reportsvolume 9, Article number: 3073 (2019

 

Abstract

 

Leigh syndrome is a mitochondrial disease characterized by neurological disorders, metabolic abnormality and premature death. There is no cure for Leigh syndrome; therefore, new therapeutic targets are urgently needed. In Ndufs4-KO mice, a mouse model of Leigh syndrome, we found that Complex I deficiency led to declines in NAD+ levels and NAD+ redox imbalance. We tested the hypothesis that elevation of NAD+ levels would benefit Ndufs4-KO mice. Administration of NAD+precursor, nicotinamide mononucleotide (NMN) extended lifespan of Ndufs4-KO mice and attenuated lactic acidosis. NMN increased lifespan by normalizing NAD+ redox imbalance and lowering HIF1a accumulation in Ndufs4-KO skeletal muscle without affecting the brain. NMN up-regulated alpha-ketoglutarate (KG) levels in Ndufs4-KO muscle, a metabolite essential for HIF1a degradation. To test whether supplementation of KG can treat Ndufs4-KO mice, a cell-permeable KG, dimethyl ketoglutarate (DMKG) was administered. DMKG extended lifespan of Ndufs4-KO mice and delayed onset of neurological phenotype. This study identified therapeutic mechanisms that can be targeted pharmacologically to treat Leigh syndrome.

https://www.nature.c...598-019-39419-4


Pretty obvious they are gearing up to try this therapy with humans who have various mito disorders. Wonder how long before human trials? 


Edited by Phoebus, 06 March 2019 - 03:09 PM.

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#2 Phoebus

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Posted 06 March 2019 - 03:26 PM

 

 

Therapeutic benefits of NMN were mediated by elevation of alpha-ketoglutarate (KG) levels and suppression of hypoxic signaling.

 

So thats the mechanism they seem to be focusing on here. 

 

 



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