uniQure’s AMT‑260 gene therapy showed seizure reductions up to 100% in early GenTLE trial data for refractory mesial temporal lobe epilepsy, supporting continued clinical evaluation.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
uniQure N.V. has reported initial six-month follow-up data from the first low-dose cohort of its ongoing Phase I/IIa GenTLE trial evaluating AMT-260, an investigational gene therapy for refractory mesial temporal lobe epilepsy (MTLE). The data were presented at the Epilepsy Foundation Pipeline Conference in Leesburg, Virginia.
Initial Results
As of the May 29, 2026 data cutoff, six patients had received AMT-260 at a dose of 1 × 10¹² gc/mL. During months four through six after treatment, three patients experienced substantial reductions in disabling seizure frequency ranging from 79% to 100% compared with baseline, including one patient who remained seizure-free during the assessment period.
Outcomes were more variable in the remaining three patients, ranging from a 33% reduction to a 36% increase in seizure frequency. Given the small sample size and limited follow-up, additional data will be needed to determine the consistency and durability of treatment effects.
Safety
AMT-260 demonstrated a favorable safety profile in the low-dose cohort. No serious adverse events related to the gene therapy or surgical procedure were reported, and no immunosuppression was required. All reported adverse events were mild to moderate, with headache reported in two patients.
According to uniQure Chief Medical Officer Walid Abi-Saab, M.D., the findings support continued clinical evaluation of AMT-260 in patients with drug-resistant epilepsy.
Next Phase of Development
Enrollment is underway in a second cohort evaluating a higher dose of 3 × 10¹² gc/mL in up to six patients. The company expects enrollment to be completed during 2026 and plans to present updated clinical results in the first half of 2027.
About the GenTLE Trial and AMT-260
The GenTLE study (NCT06063850) is an open-label, multi-center Phase I/IIa trial evaluating AMT-260 as a one-time intracerebral gene therapy administered directly into affected brain regions through a stereotactic neurosurgical procedure. The study consists of two dose cohorts of up to six patients each and includes an initial 12-month evaluation period followed by four years of long-term follow-up.
AMT-260 is designed to suppress expression of the GRIK2 gene using two engineered microRNAs. This approach reduces production of the GluK2 kainate receptor subunit, which is believed to play a key role in seizure generation in mesial temporal lobe epilepsy.
About Refractory Mesial Temporal Lobe Epilepsy
Temporal lobe epilepsy affects approximately 500,000 people in the United States, with an estimated 300,000 individuals experiencing seizures that remain inadequately controlled despite anti-seizure medications. Approximately 80% of drug-resistant cases are classified as mesial temporal lobe epilepsy, involving deep structures within the temporal lobe. While treatment options include medications and surgery, many patients continue to experience uncontrolled seizures or are not suitable candidates for surgical intervention.
What This Means for Patients
For people living with drug-resistant mesial temporal lobe epilepsy, uncontrolled seizures can affect daily activities, independence, safety, and overall quality of life despite treatment with multiple medications. Early findings from this study suggest that AMT-260 may help reduce seizure frequency in some patients, with several participants experiencing substantial improvements and one patient remaining seizure-free during the fourth through sixth months after treatment. The therapy was also generally well tolerated, with no serious treatment-related safety concerns reported. While these results are still preliminary and require confirmation in larger studies, AMT-260 offers hope for a future treatment option that could provide lasting seizure control through a single administration.
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About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office.