Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterised by the progressive loss of GABAergic medium spiny neurons (MSNs) in the striatum. The study of neurodegenerative disorders such as HD has been impaired by limited access to live human disease-affected neurons. Cellular reprogramming of patient-derived somatic cells now offers an opportunity to generate live human neurons for the study of neurological conditions. We have developed a highly efficient protocol for direct reprogramming of adult human fibroblasts (HDFs) to induced neural precursor cells (iNPs) within 21 days by co-transfection of chemically-modified mRNA (cmRNA) encoding the pro-neural transcription factors SOX2 and PAX6 in a defined reprogramming medium. Directly reprogrammed iNPs express the neural transcription factors GSX2, ASCL1, DLX2, and MEIS2, required for the development of MSNs. We have optimised this protocol to generate high yields of DARPP32+ neurons within 30 – 45 days of differentiation using a combination of growth factors and small molecules in a BrainPhysTM medium under physiological oxygen (5% O2) conditions. HDFs from patients with HD (n=4; CAG repeat lengths 41 – 57) and normal subjects (n = 4; CAG repeat lengths 18 – 34) were directly reprogrammed with cmRNA SOX2 and PAX6. The morphology of HD-derived neuronal cultures was compared to normal neuronal cultures at 30 and 45 days of differentiation. HD-derived neuronal cultures demonstrated significantly reduced neurite branching, smaller cell bodies, and shorter neurites compared to normal cultures. HD-derived neuronal cultures also demonstrated the presence of huntingtin protein aggregates. These results demonstrate that HD-derived neurons exhibit a distinct alternation in neuronal morphology compared to normal neurons, providing a novel in vitro platform for studying the pathophysiology of HD.