Introduction: Huntington's disease (HD) is an unpleasant and costly genetic disease that affects people who die 15-20 years after the onset of symptoms. HD is usually diagnosed in middle age with dementia and weight loss as well as the pathological increase in natural and voluntary functions. Huntingtin's (HTT) is a protein that causes Huntington's disease during mutation. HTT is a large, highly conserved protein that interacts with many molecules and plays a diverse role in regulating transcription, mitochondrial activity, synaptic function, and other cellular processes. Mutations in this gene cause a polyglutamine (polyQ) extension in exon 1 protein of the CAG sequence. Currently, a combination of therapies based on gene silencing, gene editing (CRISPR) and human stem cells can be useful in the treatment of this disease. Gene silencing offers a new therapeutic strategy for dominant genetic disorders. In certain diseases, selective deletion of only one copy of a gene may be beneficial for deleting both copies unselected. Using this treatment strategy and switching off the expanded version of HTT, you can get the desired results in the treatment of this disease. Currently, allele-specific methods can be stopped by targeting extended CAG repeats or single nucleotide polymorphisms (SNP) in non-expanded imbalances. This treatment requires personalized treatment strategies based on the patient's genotypes. Most gene silencing methods target or block RNA encoded by a particular gene, or block translation or reduce RNA by endogenous mechanisms by reducing mRNA transcripts that inhibit protein production they become pathogenic. Based on in vitro findings in model mice, silencing using miRNAs and specific allele silencing (SNP) targeted muHTT in siRNA-transfected cells able to reduce the HTT transcription level by approximately 80%. Another therapeutic approach in this disease is the use of CRISPR-based genome editing technology. We can modify Huntington's hiPSCs using CRISPR-Cas9 and the transposon-based selective system, which could lead to the elimination of a number of phenotypic abnormalities and gene expression changes in hiPSC-derived neurons be.
Methods: Surveying different articles related to the subject in recent years with using several internet search engines like google chrome, PubMed, and Scopus.
Results: For Huntington's (HD) treatment, gene silencing-based therapy, gene editing (CRISPR), and the use of human stem cells can provide more effective treatment for Huntington's disease. Based on this therapeutic strategy, we prevent gene expression by using gene silencing, and we rearrange the mutated allele (muHTT) by regulating gene expression and gene editing. This treatment requires a combination of gene silencing, gene editing, and stem cell therapies to obtain optimal and modifying results.
Conclusion: In summary, a review of recent papers suggests that currently the only useful therapeutic approach for the treatment of Huntington's disease is the use of combination therapy with gene silencing, CRISPR-based gene editing and the use of human stem cells. In addition, the results of studies in model mice have shown that gene silencing reduces transcription of HTT by approximately 80%. In addition, healing of motor symptoms after repair of damaged neurons can be achieved using stem cells. Stem cells can therefore differentiate into the target tissue and cell and help us cure the disease.