Gene Therapy AMT-260 Shows Early Seizure Reductions in Refractory Mesial Temporal Lobe Epilepsy, Phase 1 Cohort Data Show

In recent news, uniQure announced preliminary six-month follow-up data from the first cohort of GenTLE, a phase 1/2a trial of AMT-260, an investigational one-time gene therapy delivered directly into the hippocampus for refractory mesial temporal lobe epilepsy (MTLE).¹ The data, presented at the Epilepsy Foundation Pipeline Conference in Leesburg, Virginia on June 19, 2026, represented the first cohort-level readout from a program that has been building toward this milestone since the first patient was dosed in 2024.

The results follow an initial case study presented at the Epilepsy Therapies & Diagnostics Development Symposium in May 2025, in which the first GenTLE participant showed a 92% reduction in seizure frequency over five months of follow-up with no serious adverse events, offering the first clinical signal of activity.²

Cohort 1 Findings

As of the May 29, 2026, data cutoff, all six patients in the first, low-dose cohort (1x10¹² gc/mL) had been treated and followed for at least six months. Three of the six patients achieved meaningful reductions in disabling seizures during months four through six, with individual declines from baseline ranging from 79% to 100%. The remaining three patients showed variable responses, ranging from a 33% decrease to a 36% increase in disabling seizures during the same window.¹

“While patient responses have varied, we believe the data generated to date provide preliminary evidence of biological activity of AMT-260,” Walid Abi-Saab, MD, chief medical officer of uniQure, said in a statement.¹ “Although these findings are based on a limited number of patients and require longer follow-up, the favorable tolerability profile and observed responses support continued evaluation of AMT-260.”

No serious adverse events related to AMT-260 or the surgical delivery procedure have been reported to date. All adverse events in the low-dose cohort were mild or moderate in severity, with headache being the most common (n = 2). No immunosuppression was required, a notable finding given that AAV-based gene therapies have historically required corticosteroid protocols to manage immune responses to the viral vector.

Enrollment is ongoing in a second, higher-dose cohort (3x10¹² gc/mL) expected to consist of six patients, with enrollment anticipated to complete mid-2026. uniQure expects to present updated results from both cohorts in the first half of 2027.

Mechanism and Delivery

AMT-260 uses an AAV9 viral vector to deliver two engineered microRNAs directly into the hippocampus via MRI-guided convection-enhanced delivery (CED), a stereotactic infusion technique designed to achieve targeted distribution within the mesial temporal structures. The microRNAs are designed to suppress the GRIK2 gene, reducing expression of GluK2, a subunit of the kainate glutamate receptor believed to drive seizure generation in refractory MTLE. Unlike systemic gene therapy approaches, the intracerebral, locally administered design avoids widespread CNS biodistribution and is intended as a single lifetime administration.¹

Context and Pipeline

MTLE is the most common form of drug-resistant focal epilepsy, affecting an estimated 300,000 people in the United States inadequately controlled on anti-seizure medications. For patients who fail multiple medications, surgical options including anterior temporal lobectomy and minimally invasive alternatives such as laser interstitial thermal therapy exist, but carry risks of memory impairment and language dysfunction that lead many patients to decline or remain ineligible.³ AMT-260 is being developed for this population as a one-time molecular alternative to resection.

The GenTLE data arrive as uniQure advances its broader neurological gene therapy program. Earlier this month, the company announced that the FDA indicated 3-year phase 1/2 data from AMT-130, its investigational gene therapy for Huntington disease (HD), may support a planned Biologics License Application (BLA) submission under the accelerated approval pathway, targeted for the third quarter of 2026.⁵

At the 3-year analysis, the high-dose AMT-130 cohort demonstrated a 75% slowing of disease progression on the comprehensive Unified Huntington's Disease Rating Scale compared with a propensity score-matched external control (P = .003). Together, the AMT-130 regulatory milestone and the AMT-260 cohort data reflected the company's expanding footprint in CNS gene therapy.

The AMT-260 cohort-level data are preliminary, based on six patients with heterogeneous responses over a limited six-month window. Three patients did not achieve a meaningful response at the low dose, and whether the higher-dose cohort will produce more consistent activity remains to be seen. Longer follow-up and data from both cohorts will be required before any conclusions about efficacy can be drawn.

REFERENCES
1. uniQure announces preliminary data on the first cohort in the phase I/IIa clinical trial of AMT-260 in refractory mesial temporal lobe epilepsy. News release. uniQure N.V. June 19, 2026. Accessed June 22, 2026. https://www.globenewswire.com/news-release/2026/06/19/uniqure-amt-260-phase1-cohort-data
2. uniQure presents clinical case study of first patient dosed with AMT-260 in refractory mesial temporal lobe epilepsy (MTLE). News release. uniQure N.V. May 29, 2025. Accessed June 22, 2026. https://uniqure.gcs-web.com/news-releases/news-release-details/uniqure-presents-clinical-case-study-first-patient-dosed-amt-260
3. Jobst BC, Cascino GD. Resective epilepsy surgery for drug-resistant focal epilepsy: a review. JAMA. 2015;313(3):285-293. doi:10.1001/jama.2014.17426. https://doi.org/10.1001/jama.2014.17426
4. Marathe K, Alim-Marvasti A, Dahele K, et al. Resective, ablative and radiosurgical interventions for drug resistant mesial temporal lobe epilepsy: a systematic review and meta-analysis of outcomes. Front Neurol. 2021;12:777845. doi:10.3389/fneur.2021.777845. https://doi.org/10.3389/fneur.2021.777845
5. uniQure announces plan for BLA submission for AMT-130 in Huntington's disease. News release. uniQure N.V. June 17, 2026. Accessed June 22, 2026. https://www.uniqure.com/investors-media/press-releases