Huntington’s Disease (HD) is a human neurodegenerative disorder which leads to progressive and severe disability, characterised by motor, cognitive and behavioural dysfunctions. It is known that HD is a monogenic disease resulting in a CAG trinucleotide repeat expansion (CAG repeats) in exon 1 of the gene huntingtin. Current treatments are palliative, and no disease modifying therapies are currently available. Thus, HD remains untreatable and fatal. We have established a unique cellular model by generating striatal neurons from human induced pluripotent stem cells (hiPSC) generated from HD patients. In this study, we have employed three HD lines which express different CAG expansion lengths in their huntingtin gene – HD33, HD60 and HD109 – and generated neural progenitors using a patterning protocol described in Telezhkin et al (2015). We have recently observed that molecular and functional expression of M-type current (carried by Kv7.2/7.3 channel subunits) are dynamically regulated during striatal neuronal differentiation in vivo and in vitro and during differentiation of hiSPC in vitro, thus determining excitability. Furthermore, neurons generated from HD hiPSC neurons demonstrate defective excitability parameters (Telezhkin, Yarova, Allen and Kemp, unpublished) and M-type current is defective in an HD mouse model (Cao Y et al., PNAS, 2015). Thus, we have tested the hypothesis that chronic pharmacological upregulation of M-type current will result in functional rescue of impaired function seen in HD patient, hiPSC-derived striatal neurons during three week differentiations from neural precursors. In HD33 neurons, M-current activation by flupirtine only slightly shifted Vm from -42.4 ± 1.9 mV (n = 10) to -44.7 ± 2.0 mV (n = 10), whereas M-current inhibition with XE991 significantly depolarized Vm to -30.9 ± 2.4 mV (n = 10, p < 0.01). Similarly, in HD60 neurons, flupirtine shifted Vm only modestly from -45.0 ± 2.6 mV (n = 12) to -48.1 ± 2.2 mV (n = 14), whilst XE991 significantly depolarized Vm to -36.5 ± 1.5 mV (n = 12), p < 0.01). In HD109 neurons, flupirtine treatment resulted in insignificant shift of Vm from -38.1 ± 1.7 mV (n = 26) to -39.3 ± 1.4 mV (n = 23) and XE991 produced significant change in Vm -33.1 ± 1.7 mV (n = 25, p < 0.05). Values are means ± SEM, statistics is done with unpaired t-Test. Such alterations in Vm broadly mapped onto parallel changes in excitability. Thus, upregulation of M-channels, via pharmacological manipulation, partially rescues the depressed excitability seen during differentiation of HD hiPSC-derived neurons. This is especially exciting because M-current activator flupirtine is already in clinical practice for the treatment of another central neuronal disorder, meaning that these drugs could be repurposed to enhance striatal function in early diagnosed HD patients HD, perhaps delaying the progression of this fatal neurodegenerative condition.