Desarrollo de Fármacos

Área de la Ciencia:

• Neuroscience
• Gene Therapy
• Neurology

Sus antecedentes:

• Brain-Derived Neurotrophic Factor (BDNF) is crucial for neuronal survival, function, and cognitive processes.
• Animal models of Alzheimer's disease (AD) show BDNF gene delivery improves cognitive performance.
• Previous studies demonstrated BDNF's benefits in preclinical models, supporting its advancement to human trials.

Objetivo del estudio:

• To evaluate the safety and efficacy of AAV2-BDNF gene delivery in patients with biomarker-supported mild AD and Mild Cognitive Impairment (MCI).
• To assess the impact of AAV2-BDNF gene therapy on cognitive function and brain metabolism in AD and MCI patients.

Principales métodos:

• A Phase 1 clinical trial involving MRI-guided injection of AAV2-BDNF into the entorhinal cortex.
• Recruitment of 12 patients (6 mild AD, 6 MCI) monitored over 2 years.
• Serial cognitive testing and Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scans for monitoring.

Principales resultados:

• AAV2-BDNF gene therapy was administered to 6 mild AD patients with follow-up up to 18 months.
• No serious adverse events related to the AAV2-BDNF treatment were reported.
• FDG-PET scans in three patients treated for at least 6 months showed increased cortical metabolism in the entorhinal cortex, reversing the typical AD decline.

Conclusiones:

• AAV2-BDNF gene therapy delivered to the entorhinal cortex is safe in mild AD patients.
• The treatment restored metabolic activity in the targeted brain region, as evidenced by FDG-PET scans.
• BDNF gene therapy presents a potential neuro-restorative approach for AD and MCI by preventing neuronal loss and enhancing function.