LEXINGTON, Mass. & AMSTERDAM | June 19, 2026
uniQure N.V. has announced preliminary six-month follow-up data from the first low-dose cohort of its ongoing Phase I/IIa GenTLE clinical trial evaluating AMT-260, an investigational one-time gene therapy for refractory mesial temporal lobe epilepsy (MTLE). The early findings, presented at the Epilepsy Foundation Pipeline Conference in Leesburg, Virginia, indicate that AMT-260 was generally well tolerated, with no serious adverse events (SAEs) or surgery-related complications reported to date. Importantly, several participants demonstrated encouraging reductions in disabling seizures, providing early biological evidence of potential therapeutic activity. Although based on a small patient population, the results support continued clinical development of AMT-260 as a potential disease-modifying treatment for patients with epilepsy who do not respond adequately to available anti-seizure medications.
Three Patients Achieved Major Seizure Reductions
Based on the May 29, 2026 data cutoff, three of the six patients treated in the first low-dose cohort (1×10¹² gc/mL) experienced substantial reductions in disabling seizures during months four through six after treatment, ranging from 79% to 100% below baseline. The remaining three participants showed more variable clinical outcomes, with seizure frequency ranging from a 33% reduction to a 36% increase compared with baseline. While patient responses differed, investigators noted that the observed improvements in several participants provide encouraging evidence that AMT-260 may influence the biological mechanisms underlying seizure generation. The therapy also demonstrated a favorable safety profile, with all reported adverse events classified as mild or moderate, and headache being the most frequently reported event. Notably, no immunosuppressive therapy was required following treatment, supporting the investigational therapy’s tolerability.
Gene Therapy Targets the Underlying Cause of MTLE
AMT-260 is designed as a single-administration in vivo gene therapy that delivers two engineered microRNAs directly into the brain through a localized intracerebral infusion. The therapy aims to suppress the GRIK2 gene, reducing abnormal expression of the GluK2 kainate receptor subunit, which is believed to contribute to seizure activity in patients with refractory mesial temporal lobe epilepsy. Unlike conventional anti-seizure medications that primarily manage symptoms, AMT-260 seeks to address a key molecular driver of epilepsy, potentially offering a long-lasting therapeutic effect after just one treatment. Approximately 500,000 people in the United States live with temporal lobe epilepsy, with nearly 300,000 remaining inadequately controlled despite available medications, highlighting the significant unmet medical need for innovative therapeutic approaches.
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Higher-Dose Cohort Enrollment Continues
Following the encouraging preliminary safety and efficacy observations, uniQure continues enrollment in the second, higher-dose cohort (3×10¹² gc/mL) of the Phase I/IIa GenTLE study, which is expected to include an additional six patients. Enrollment is anticipated to be completed by mid-2026, with updated clinical results expected during the first half of 2027. The multi-center, open-label study includes a 12-month primary evaluation period followed by four years of long-term follow-up to assess the durability of treatment response and long-term safety. As one of several gene therapy programs within uniQure’s neurological disease pipeline, AMT-260 represents an innovative effort to develop potentially transformative treatments for patients with severe, treatment-resistant epilepsy and other serious neurological disorders where current therapeutic options remain limited.
Source: uniQure press release
