Treating ALS disease by rescuing interneuron-motor neuron synaptic connectivity
In ALS, spinal inhibitory interneurons lose their connections to motor neurons during early pre-symptomatic stages before motor neuron death. The loss of these synaptic inputs appears to be restricted to vulnerable motor neurons and triggers pathological events such as, increased intracellular Ca2+ levels, ER stress and cell death. This project aims to rescue the synaptic connections between interneurons and motor neurons in an ALS mouse model by gene therapy, to understand if this alone could reverse the symptoms. This project is conducted in collaboration with the Verhaagen laboratory at the Netherlands Institute for Neuroscience and funded by the Lundbeck foundation, the Danish Society for Neuroscience-Lundbeck scholarships, and University of Copenhagen.
Dissecting the role of inhibitory and excitatory spinal interneurons in ALS pathology
This project aims to clarify the contribution of inhibitory and excitatory spinal interneurons to ALS pathophysiology. Here, multiplexing detection of transcripts is combined with machine learning-based cell segmentation and bioinformatic analysis to understand the degeneration of specific neural circuits within the spinal cord. This project is conducted at University of Copenhagen in collaboration with Prof. Ole Kiehn, Dr. Raghavendra Selvan and ACD Bio. It is funded by the Lundbeck foundation (IA), the Novo Nordisk foundation (OK), the Louis-Hansen Foundation (RM), ACD Bio and the Department of Neuroscience.
Investigating the causes of V1 interneuron dysregulation in early stages of ALS using spatial transcriptomics
The loss of synaptic inputs detected in pre-symptomatic ALS mice might be due to alterations occurring either in the inhibitory interneurons or in the motor neurons. To understand the temporal dynamics of this event, spatial transcriptomics is applied to investigate the role of motor neuron and interneurons during degeneration. This project is conducted at University of Copenhagen in collaboration with Nanostring and the Department of Molecular Medicine (MOMA) at Aarhus University Hospital. It is funded by the Louis-Hansen Foundation and the Danish Society for Neuroscience-Lundbeck scholarships.
Facing dementia: investigating early onset of Frontotemporal Dementia via Artificial Intelligence
Artificial intelligence (AI)-based methods are applied to identify emotions in a mouse model of FTD in response to positive or adverse stimuli delivered by a virtual reality (VR) interface. Correlations between early FTD symptoms and alterations in the activity of neural circuits found in the frontal and prefrontal lobes of the brain are investigated to find new targets for treatment. This project is conducted at University of St Andrews in collaboration with Dr. Raghavendra Selvan at the Machine Learning Section, Department of Computer Science (University of Copenhagen). It is funded by the University of St Andrews and the St Leonard’s Postgraduate College.
Amyotrophic Lateral Sclerosis, treating the circuit behind the disease
The overall purpose of this project is to develop a translational gene therapy. This project is conducted at University of Copenhagen in collaboration with the Bispebjerg Brain Bank, together with Dr. Susana Aznar and Dr. Kirsten Svenstrup. This project is supported by seed funding obtained from the Danish ALS Society and the Læge Sophus Carl Emil Friis og Hustru Olga Doris Friis’ Legat.