Treating Alzheimer's disease by characterising and repairing circuit activity using GENUS therapy

About this project

<table align="center" style="width: 1630.67px; border-collapse: collapse" border="0" cellspacing="0" cellpadding="3"> <tbody> <tr> <td style="border-color: #EEEEEE; height: 25px"> <p style="text-align: justify"><span style="font-size: 12px">Alzheimer’s disease (AD) is a neurodegenerative disease for which there is no cure. Decades of research have revealed the unique genetic, molecular and cellular pathology of AD. However, largely due to a lack of techniques enabling the precise measurement of neural circuit activity in vivo, we know little about how it affects the high-level processing that underlies cognitive functions such as memory and spatial navigation. To address this gap in knowledge, our first aim is to capitalize on recent technical developments in our labs to measure activity of thousands of neurons simultaneously in AD mice that are trained to perform a cognitive task. We will focus on a cortical area called the retrosplenial cortex (RSC), a key brain structure for memory and navigation and an early target of AD. A second aim is to test and further develop a novel and highly-promising therapy that significantly improves memory in mouse models of the disease. By presenting multisensory stimuli (visual and auditory) at 40 Hz to restore gamma oscillations in the cortex, this therapy (acronym: GENUS) reduces extracellular peptide aggregates and significantly improves cognition. We will use this therapy to test whether the improvements in cognition are mirrored by a restoration of relevant microcircuit function in RSC. A third major aim is to develop a new device, called GAMMAHEAL, to dynamically optimise the multisensory stimuli by using real-time feedback information from cortical rhythms. We will apply this closed-loop stimulation platform in mice and humans, and develop it such that, at project completion, it is ready to be applied in human AD patients.</span></p> </td> </tr> </tbody> </table>

Bilateral cooperation results

Our team has filed an international joint patent for GAMMAHEAL with the World International Property Organization (WIPO) in Geneva. We plan to further develop this technology, aiming for clinical validation and commercialization through a Romanian startup. This startup will collaborate with clinical partners to provide non-invasive, low-cost AD treatment, potentially reducing Romania’s innovation gap with the EU. CIRCUITGENUS has strengthened bilateral relations, continuing a tradition of collaboration between the Mureșan lab and Norwegian partners. The project has enhanced the partnership between the Mureșan and Vervaeke labs, combining engineering and data analysis expertise with experimental design and behavioural testing. This collaboration successfully developed a robust GAMMAHEAL stimulation methodology, and facilitated new partnerships, such as those with the Glia Lab in Oslo, but also labs in Hungary and Belgium in a consortium with the University of Oslo.

Project partners

• University of Oslo Donor project partner· Norway