Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by an extended poly-glutamine tract in the huntingtin gene (HTT). Despite intensive efforts in understanding its pathogenesis over the decades, effective treatments for HD remain unavailable. The aim of this thesis was to explore new therapeutic strategies for HD via two approaches. The first approach was based on an active vaccination strategy using SupraAntigen™ technology. To this end, vaccines targeting different regions of HTT exon 1 were generated and tested for their potency to induce an antibody response and modify pathological progression in HD model mice. The second approach was based on the identification of small molecular weight chemicals that were inhibitors of mutant HTT oligomerization. To this end, various biochemical assays were established to study mutant HTT assemblies in the presence of novel compounds. Compound ACI-695 progressed to an in vivo efficacy study in HD model mice. Our studies provided new research tools for HD pathogenesis investigation and highlighted the possibility of using immune therapy and small molecules as modifiers for HD progression.