Gene Editing and Silencing
- CRISPR Base Editing: In vivo CRISPR tools correct CAG repeats in mouse models, reducing mutant huntingtin levels without cutting DNA .
- Artificial miRNAs: AAV-delivered miRNAs suppress mutant HTT in sheep striatum, a milestone for gene-silencing therapies .
Metabolic Interventions
- 3-Hydroxybutyrate (3-HB): This ketone body improves mitochondrial function and histone acetylation in HD mice, delaying motor deficits .
Table 3: Emerging HD Therapies
| Therapy | Mechanism | Stage of Development |
|---|---|---|
| CRISPR base editing | Corrects CAG repeats | Preclinical (mice) |
| AAV-miRNA | Silences mutant HTT | Large animal trials |
| 3-HB infusion | Boosts mitochondrial function | Preclinical (mice) |
Caption: Promising therapies targeting HD’s genetic and metabolic roots .
Ethical and Social Dimensions
Predictive genetic testing for HD poses profound dilemmas. While testing can alleviate uncertainty, it also risks psychological distress and identity crises. Studies highlight the need for personalized counseling, as decisions often hinge on family planning and coping capacity .
Conclusion: Hope on the Horizon
HD research has transformed our understanding of genetic diseases, revealing the interplay of DNA instability, protein toxicity, and metabolic dysfunction. With CRISPR, miRNAs, and metabolic therapies entering clinical pipelines, the future holds unprecedented promise. By decoding HD’s genetic mysteries, we inch closer to not only curing this disease but also unlocking insights into broader neurodegenerative disorders.