Reduction in urinary oxalate excretion in mouse models of Primary Hyperoxaluria by RNA interference inhibition of liver lactate dehydrogenase activity

CRISPR/Cas9–mediated metabolic pathway reprogramming in a novel humanized rat model ameliorates primary hyperoxaluria type 1

“…17 However, lactate dehydrogenase inhibition has triggered significant changes in liver glycolytic and b a s i c r e s e a r c h tricarboxylic acid cycle metabolites, and the safety of this strategy should be further investigated. 31 The advantage of RNA interference strategy is the transient reduction of Hao1 expression, which is reversible when the drug is no longer being taken. [14][15][16] However, it requires repetitive administration.…”

The Handling of Oxalate in the Body and the Origin of Oxalate in Calcium Oxalate Stones

“…PH I, accounting for the majority of all cases (70-80%) [38], is a peroxisomal disease and the most severe type. It is caused by mutations in AGT [39], a peroxisomal enzyme located in the liver; it is a genetic defect disease and it is inherited with an autosomal recessive pattern. Mutation or the absence of AGT resulting in a severe reduction of AGT enzymatic activity in the peroxisome produces more glyoxylate aggregation which is metabolized to oxalate via glycolate oxidase or lactate dehydrogenase, leading to hyperoxaluria.…”

Knockdown of lactate dehydrogenase by adeno‐associated virus‐delivered CRISPR/Cas9 system alleviates primary hyperoxaluria type 1

“…Recent therapeutic advances involve targeting PH1 at the genetic and molecular level through substrate reduction therapy (SRT), which alleviates PH1 through inactivation of either glycolate oxidase (GO) (EC 1.1.3.15) that produces glyoxylate or LDH that catalyzes glyoxylate into oxalate. [6][7][8][9][10] By comparing the effect of targeting LDH versus GO through RNA interference (RNAi), it has been demonstrated that compared with GO, less reduction of LDH protein was required to reduce oxalate production. 9 Furthermore, a phase I clinical trial of LDH inhibition has shown encouraging preliminary results (NCT03392896).…”