Composition for preventing or treating neurodegenerative diseases comprising a miRNA inhibitor and uses thereof

ALS therapeutic agent restoring microglial phagocytosis and autophagy using a miRNA-214-3p inhibitory oligonucleotide

This technology is a pharmaceutical composition for preventing or treating amyotrophic lateral sclerosis (ALS) that uses a miRNA-214-3p inhibitor consisting of the oligonucleotide of SEQ ID NO: 2 as an active ingredient. It also encompasses health functional food compositions and pharmaceutical formulations containing the same inhibitor, as well as methods of treatment for non-human subjects.

While the number of patients with neurodegenerative diseases such as ALS, Alzheimer's, and Parkinson's is rapidly increasing due to aging, these conditions have lacked curative treatments. Once damaged, neurons are difficult to recover, leading to progressive symptom deterioration, and the exact causes remain unclear. Existing treatments only slow disease progression, and although differential miRNA expression has been reported in patient bodily fluids, no therapeutic agents directly targeting miRNAs have been attempted.

This technology inhibits miRNA-214-3p to simultaneously regulate the expression of its targets: microglial phagocytosis factors (NCKAP1, WASF2, ABL2), neuroinflammatory factors (TRAF1, TNFSF10, IKBKB), autophagy factors (RUBCN, ATG16L1, ATG12), and nucleocytoplasmic transport factors (TNPO1, IPO11, KPNA1). This restores microglial function in clearing protein aggregates, reduces neuroinflammation, and aids in the resolution of pathological aggregates. Applicable to antisense nucleic acid therapies for ALS, RNA-based drug pipelines for neuroinflammation, and animal models of neurodegeneration, this approach enables a multi-target therapeutic strategy that corrects multiple pathological pathways—phagocytosis, inflammation, autophagy, and nuclear transport—by inhibiting a single miRNA.

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Key Features:

• Pharmaceutical composition for preventing or treating ALS comprising a miRNA-214-3p inhibitor, which is an oligonucleotide consisting of SEQ ID NO: 2, as an active ingredient
• Health functional food composition for preventing or improving ALS comprising a miRNA-214-3p inhibitor as an active ingredient
• Pharmaceutical formulation for preventing or treating ALS comprising a miRNA-214-3p inhibitor consisting of the oligonucleotide of SEQ ID NO: 2 as an active ingredient
• Step of preventing or treating ALS by administering a pharmaceutical composition containing a miRNA-214-3p inhibitor to a non-human subject

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This invention was developed with support from the Ministry of Science and ICT for the establishment of a novel dementia pathogenesis and personalized treatment strategy platform using patient-specific microglial models.

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