Target intelligence / Profile preview

Lactate dehydrogenase A messenger RNA (LDHA mRNA) (LDHA mRNA)

Target
LDHA mRNA
Molecular classification
Messenger RNA, Nucleic acid
01

Overview

Lactate dehydrogenase A (LDHA) messenger RNA is the nucleic acid transcript that encodes the LDHA enzyme, a key protein involved in the final step of anaerobic glycolysis and the conversion of glyoxylate to oxalate in the liver (PMID: 34403573). In patients with Primary Hyperoxaluria Type 3 (PH3), mutations in the HOGA1 gene lead to an accumulation of glyoxylate, which the LDHA enzyme then converts into toxic oxalate (FDA, 2023). By targeting the LDHA mRNA specifically, therapeutic agents can reduce the overall production of the LDHA protein, thereby lowering oxalate levels and preventing kidney stone formation and renal damage. The primary drug interacting with this target is nedosiran, a small interfering RNA (siRNA) that utilizes the cellular RNA interference machinery to degrade the LDHA transcript in hepatocytes (PMID: 37553344). Beyond metabolic disorders, LDHA mRNA is frequently overexpressed in various malignancies to facilitate the Warburg effect, where cancer cells prioritize glycolysis for energy production even in aerobic conditions (PMID: 27013337). Consequently, LDHA mRNA represents a significant target for both rare metabolic diseases and potential oncology applications.

Other names
LDHA transcriptL-lactate dehydrogenase A chain mRNALactate dehydrogenase A mRNA
02

Mechanism of action

RNA interference (RNAi) mediated degradation of the mRNA transcript via the RISC complex, preventing the translation of the LDHA protein (PMID: 37553344).

03

Biological functions

TranslationMetabolic regulationGlyoxylate metabolismAnaerobic glycolysis
04

Disease associations

Primary hyperoxaluria type 3CancerHyperoxaluriaUrolithiasis
05

Safety considerations

Injection site reactionsPotential for transient liver enzyme elevationsLong-term metabolic consequences of systemic LDH reduction
06

Interacting drugs

Nedosiran
07

Biomarkers

Urinary oxalate levelsPlasma oxalate levelsLDHA protein expression

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