Abstract
Over the last years, an increased interest in pharmacological and non-pharmacological therapeutic approaches have increased in HD research, at the moment HD remains a non-curable disease and current approaches involve symptomatic disease treatment. The systematic review identifies studies that have investigated pharmacological and non-pharmacological interventions, in HD individuals and mouse models to identify the clinical impact, regarding i) silencing and reduction of mHTT, ii) safety, efficiency and toxicity of antisense nucleotides, zinc finger proteins, CRISPR-Cas9 and transcription activator-like effector nuclease, iii) genetic modifiers contributing to early or delayed HD onset and, iv) importance of physical activity on motor and cognitive function. A systematic search of PubMed and Directory of Open Access Journal was performed by two independent reviewers using specific search term criteria for studies. The search period included studies from 2000 until 2024. The identified abstracts were screened and studies within the review fulfilled predetermined inclusion criteria. Furthermore, reference screening of included studies was also conducted. A total of forty-two studies were included. Most pharmacological studies identified that oligonucleotides, zinc finger proteins and transcription activator-like effector nuclease, reduced mHTT and HD mRNA, decreased toxicity and allele-specific targeting to prevent wild-type HTT targeting. In addition, studies involving medication such as Tetrabenazine showed to suppress HD-related chorea symptoms, while Atomoxetine did not suppress symptoms and Pridopidine showed an efficiency regarding motor symptoms. The safety and efficacy of these drugs are similar to that of other studies. Physical activity studies demonstrated that HD patients showed improvement in their gait and motor functions, an increase in cognitive function and quality of life, and a decrease in anxiety and depression, this indicates the beneficial health effects of physical activity in HD. However, further research is required to assess the full impact of pharmacological and non-pharmacological approaches in larger clinical trials assessing safety, feasibility and efficacy within HD mouse models and the HD population.