uniQure Doses First Patient in GenTLE Phase I/IIa Trial of AMT-260 for Refractory Mesial Temporal Lobe Epilepsy

On November 21, 2024, uniQure N.V. (NASDAQ: QURE), a prominent gene therapy company, announced the commencement of the GenTLE Phase I/IIa clinical trial for AMT-260, aimed at treating refractory mesial temporal lobe epilepsy (MTLE). This marks a significant step forward for the company, which has initiated three clinical trials in the past half-year.

Dr. Walid Abi-Saab, the chief medical officer of uniQure, highlighted the importance of this development. He noted that a substantial portion of patients experiencing focal onset seizures do not respond to existing treatments, leaving them with limited options. AMT-260, a one-time treatment, could potentially revolutionize the therapeutic landscape for these patients. The company is actively screening candidates for the trial and anticipates providing updates in the coming year.

AMT-260 employs an AAV9 vector to deliver two engineered miRNAs locally. These miRNAs are designed to decrease the expression of GluK2 protein subunits, a type of glutamate receptor believed to be overexpressed in the hippocampus of patients with refractory MTLE, thus triggering seizures. Preclinical studies in animals have shown that AMT-260 can reduce the daily number of seizures in a dose-dependent manner. Furthermore, it has been effective in decreasing the expression of GluK2 mRNA and protein in the hippocampus of epileptic mice and in resected hippocampal slices from patients with refractory MTLE.

The GenTLE trial is a Phase I/IIa multi-center, open-label study being conducted in the United States. It aims to assess the safety, tolerability, and preliminary efficacy of two doses of AMT-260 in individuals with refractory MTLE. Two groups of six patients each will be treated, and the trial is actively recruiting at ten sites, with two additional sites expected to be operational by the end of 2024. More information is available on clinicaltrials.gov (NCT06063850).

Temporal lobe epilepsy is a prevalent neurological disorder, being the most common form of focal epilepsy, affecting over 600,000 people in the United States. Approximately 80% of these cases are mesial, involving the brain's medial structures. The majority of MTLE cases are resistant to anti-seizure medications, significantly limiting treatment options.

uniQure aims to reshape the future of medicine by developing transformative cures. The company has already achieved a significant milestone with the approval of its gene therapy for hemophilia B, a breakthrough based on over a decade of research and clinical work. This approval represents a major advancement in genomic medicine, offering a new treatment paradigm for hemophilia patients. Utilizing its proven technology and manufacturing platform, uniQure is advancing a pipeline of proprietary gene therapies targeting Huntington's disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe conditions.