Advances in Stem Cell Therapy for Huntington's Disease: A Comprehensive Literature Review

Huntington's disease (HD) is an inherited neurodegenerative disease characterized by uncontrolled movements, emotional disturbances, and progressive cognitive impairment. It is estimated to affect 4.3 to 10.6 per 100,000 people worldwide, and the mean prevalence rate among all published studies, reviews, and genetic HD registries is 5.7 per 100,000. A key feature of HD is the loss of striatal neurons and cortical atrophy. Although there is no cure at present, the discovery of the gene causing HD has brought us into a new DNA era and therapeutic advances for several neurological disorders. PubMed was systematically searched using three search strings: '"Huntington disease" + "stem cell"', '"Huntington disease" + Mesenchymal stromal cell', and '"Huntington disease" + "induced pluripotent stem cell"'. For each string, the search results were categorized based on cell type, and papers that included a clinical analysis were categorized as well. The data were extracted up to 2024. We did not include other databases in our search to have a comparable and systematic review of the literature on the topic. The collected data were analyzed and used for critical interpretation in the present review. Data are presented chronologically as clinical studies were published. Therapeutic strategies based on stem cells have drawn a lot of interest as possible HD therapies. Recent research indicates that NSCs have been the most often utilized stem cell type for treating HD. NSCs have been generated and extracted from a variety of sources, including HD patients' somatic cells and the brain itself. There is strong evidence supporting the transplantation of stem cells or their derivatives in HD animal models, even if stem-cell-based preclinical and clinical trials are still in their early stages. Current treatment only aims at relieving the symptoms rather than treating the pathogenesis of the disease. Although preclinical trials in HD models have shown promise in improving cognitive and motor functions, stem cell therapy still faces many challenges and disadvantages including immunosuppression and immunorejection as well as ethical, technical, and safety concerns. Further research is required for a definitive conclusion.