uniQure Doses First Patient in Phase I/IIa Trial of AMT-260 for Refractory Mesial Temporal Lobe Epilepsy
Key Insights
uniQure initiated the GenTLE Phase I/IIa clinical trial of AMT-260, a gene therapy for refractory mesial temporal lobe epilepsy (search) (MTLE).
AMT-260 uses an AAV9 vector to deliver engineered miRNAs, reducing GluK2 (search) protein expression in the hippocampus to decrease seizure activity.
The multi-center, open-label trial will assess the safety, tolerability, and efficacy of two AMT-260 doses in patients with refractory MTLE.
uniQure N.V. (NASDAQ: QURE) has announced the dosing of the first patient in its GenTLE Phase I/IIa clinical trial evaluating AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (search) (MTLE). The trial is designed to assess the safety, tolerability, and preliminary efficacy of the gene therapy in patients with MTLE who have not responded to conventional treatments.
Targeting GluK2 Expression
AMT-260 is composed of an AAV9 vector that delivers two engineered microRNAs (miRNAs) designed to reduce the expression of the GluK2 (search) protein subunit. GluK2, a subtype of glutamate receptor, is believed to be overexpressed in the hippocampus of individuals with refractory MTLE, contributing to seizure activity. The therapy aims to address the underlying cause of seizures by reducing the levels of this protein.
Preclinical Evidence
In preclinical animal studies, AMT-260 demonstrated a dose-dependent reduction in the number of seizures per day. Furthermore, it reduced the expression of GluK2 (search) mRNA and protein in the hippocampus of epileptic mice and in resected hippocampal slices from patients with refractory MTLE. These findings suggest that AMT-260 has the potential to modify the course of MTLE by targeting GluK2 expression.
GenTLE Trial Design
The GenTLE trial is a Phase I/IIa multi-center, open-label study conducted in the U.S. It will evaluate two dose cohorts, each consisting of six patients with refractory MTLE. The primary objectives of the trial are to assess the safety and tolerability of AMT-260. Exploratory efficacy endpoints will also be evaluated. The trial is actively recruiting patients across 10 sites, with plans to activate two additional sites by the end of 2024. Further details about the trial can be found on www.clinicaltrials.gov (NCT06063850).
The Need for New Therapies in MTLE
Temporal lobe epilepsy (search) is a chronic neurological disorder and the most common form of focal epilepsy, affecting over 600,000 individuals in the United States. Approximately 80% of temporal lobe epilepsy cases are mesial, involving the internal structures of the brain. A significant proportion of MTLE cases are refractory to anti-seizure medications, highlighting the need for new therapeutic options. "Nearly one-third of people experiencing focal onset seizures do not respond to currently available treatments and are left with limited therapeutic options," stated Walid Abi-Saab, M.D., chief medical officer of uniQure. "Our investigational agent, AMT-260, which is a one-time administration, has the potential to be a transformative treatment option for these patients."