Exploration of Neuroprotective Therapy

Table 1

Current approaches for repeat expansion diseases

Therapeutic approach	Description	Diseases targeted	References
Gene silencing therapies
Antisense oligonucleotides (ASOs)	Synthetic strands of nucleic acids targeting specific RNA to degrade or prevent translation.	HD, SCA3, C9ORF72 mediated ALS/FTD, SBMA, DM1	[4–20]
RNA interference by siRNA	Uses siRNA to degrade mRNA encoding toxic proteins.	DM1, HD, C9ORF72 mediated ALS/FTD	[21–29]
RNA interference by miRNA	Uses miRNA to degrade mRNA encoding toxic proteins.	HD, SBMA	[15, 30–34]
CRISPR/Cas9 gene editing
Direct repeat excision	Excises expanded repeat sequences using CRISPR/Cas9.	HD, SCA, DM1	[35–40]
Base editing	Alters specific nucleotides in expanded repeats without creating double-stranded breaks.	HD	[41–43]
Small molecule therapies
RNA repeats or transcription factor binding molecules	Small molecules bind expanded RNA repeats or transcription factors to prevent toxic RNA foci formation.	DM, HD	[44–46]
Proteostasis regulators	Enhance degradation of toxic proteins via the proteasome or autophagy pathways.	HD	[47–53]
Gene therapy
Gene replacement	Introduces functional copies of affected genes.	SBMA, DM	[54–56]
Regulatory element modification	Modifies regulatory elements to upregulate normal alleles or downregulate mutant ones.	FXS	[57]
Modulating toxic protein aggregation
Heat shock proteins (HSPs)	Enhance protein folding and clearance of misfolded proteins.	HD	[58]
Chemical chaperones	Stabilize protein structures to prevent toxic aggregation.	HD	[59–63]

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HD: Huntington’s disease; SCA3: spinocerebellar ataxia type 3; ALS/FTD: amyotrophic lateral sclerosis/frontotemporal dementia; SBMA: spinal and bulbar muscular atrophy; DM1: myotonic dystrophy type 1; FXS: fragile X syndrome