uniQure's AMT-260: A Promising Gene Therapy for Refractory Epilepsy

uniQure N.V. (NASDAQ: QURE), a leading gene therapy company, has announced the dosing of the first patient in the GenTLE Phase I/IIa clinical trial of AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (MTLE). This marks a significant milestone in the development of a potential transformative therapy for patients with this severe neurological disorder.

MTLE is a chronic neurological disorder affecting over 600,000 individuals in the United States alone, with approximately 80% of cases being mesial. The majority of MTLE cases are refractory to anti-seizure medications, leaving patients with limited therapeutic options. uniQure's AMT-260 aims to address this unmet need by targeting the underlying cause of seizures in MTLE patients.

AMT-260 consists of an adeno-associated virus serotype 9 (AAV9) vector that locally delivers two engineered microRNAs (miRNAs) designed to reduce the expression of GluK2 protein subunits. GluK2 is a subtype of glutamate receptor that is believed to be aberrantly expressed in the hippocampus of patients with refractory MTLE and triggers their seizure activity. Preclinical studies have shown that AMT-260 reduces the number of seizures per day in a dose-dependent manner and decreases GluK2 mRNA and protein expression in the hippocampus of epileptic mice and 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 U.S. to evaluate the safety, tolerability, and exploratory signs of efficacy of two doses of AMT-260 in individuals with refractory MTLE. The study comprises two dose cohorts of six patients each, with an additional two sites expected to be activated by the end of 2024. The study is actively recruiting through 10 sites, with additional details available on www.clinicaltrials.gov (NCT06063850).

uniQure's mission is to reimagine the future of medicine by delivering innovative cures that transform lives. The recent approvals of their gene therapy for hemophilia B represent a major milestone in the field of genomic medicine and usher in a new treatment approach for patients living with hemophilia. By leveraging their modular and validated technology and manufacturing platform, uniQure is advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory mesial temporal lobe epilepsy, amyotrophic lateral sclerosis (ALS), Fabry disease, and other severe diseases.

The potential market for AMT-260 is substantial, given its one-time administration and transformative treatment option for patients with refractory MTLE. As the first patient is dosed in the GenTLE Phase I/IIa clinical trial, investors should monitor the progress of this innovative approach, as it could open new avenues for treating refractory MTLE.



In conclusion, uniQure's AMT-260 gene therapy offers a promising approach to treating refractory mesial temporal lobe epilepsy, a severe neurological disorder with a significant unmet need. With its innovative use of an AAV9 vector to deliver engineered miRNAs targeting GluK2 protein expression, AMT-260 has the potential to transform the treatment landscape for MTLE patients. As the GenTLE Phase I/IIa clinical trial progresses, investors should closely follow the developments, as this gene therapy could represent a valuable addition to the market for refractory epilepsy treatments.