Safety and Efficacy of iPSC-Derived GABAergic Interneurons for Unilateral MTLE

ImportanceEpilepsy is one of the most common neurological disorders globally. A significant proportion of patients fail to achieve effective seizure control with medication and ultimately develop drug-resistant epilepsy, particularly mesial temporal lobe epilepsy (MTLE). While surgical resection and laser interstitial thermal therapy (LITT) are effective treatments for drug-resistant MTLE, these procedures may be associated with severe adverse events. In contrast, allogeneic induced pluripotent stem cell (iPSC)-based therapy is expected to offer a novel, potentially safer therapeutic approach with fewer side effects for patients with drug-resistant MTLE. ObjectiveTo evaluate the safety and preliminary efficacy of a single intracranial injection of ALC05 (iPSC-derived GABAergic interneurons) in patients with unilateral MTLE, and to assess the therapeutic effects of different dosage levels. Design, Setting, and ParticipantsThis single-center, randomized, double-blind, Phase 1 clinical trial will enroll 12 subjects with unilateral MTLE. All subjects will be randomly assigned to either the low-dose or high-dose group in a 1:1 ratio. To minimize risks at each dose level, the first subject in each dose group will be monitored for safety for at least 3 months following ALC05 injection and must demonstrate acceptable safety and tolerability before the remaining subjects are enrolled. The primary outcome will be the incidence and severity of adverse events (AEs) and serious adverse events (SAEs). Secondary outcomes include cell engraftment and survival, responder rate, and seizure frequency. The follow-up period for this study is 1 year. After completing the follow-up period within this study, subjects will enter a 15-year long-term safety follow-up. DiscussionMTLE remains a significant challenge in neurology. The results of this study will provide critical data regarding the feasibility and preliminary efficacy of ALC05 in treating MTLE and may offer a transformative therapeutic option for this condition.