Identifying new molecular targets for the treatment of motor neuron diseases – Eva Hedlund's research

Our research

Neurodegenerative diseases are characterized by the selective loss of specific neuronal populations with corresponding distinct clinical features. Why specific neuron types are selectively vulnerable to a neurodegenerative disease process, such as motor neurons in amyotrophic lateral sclerosis (ALS) or dopamine neurons in Parkinson’s disease (PD), is currently unclear. It is particularly intriguing as disease-causative genes are often broadly expressed in the nervous system and sometimes even in every cell in our body.

We are focused on understanding mechanisms of selective neuronal vulnerability and resilience seen in neurodegenerative diseases, with particular emphasis on the lethal motor neuron disease ALS. We believe that investigating cell intrinsic properties of neurons that show either extreme vulnerability or particular resilience and even regenerative properties in response to disease could reveal mechanisms that can be targeted by gene therapy approaches to render neurons more resistant.

Towards this purpose we have developed a method (LCM-seq) that allows for spatial RNA sequencing at the single cell level of partially degraded human tissues with exceptional sensitivity and gene detection. We are now using LCM-seq to unravel motor neuron diversity in the human spinal cord as well as to deduce the response of individual neuron to disease as these are either degenerating, persisting or regenerating in response to ALS.