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Project

The ephrin axonal repellent system in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a disease of motor nerves, leading to muscle weakness and atrophy. It is rapidly progressive and fatal within three to five years. We have previously demonstrated that EphA4 is a modifier of ALS: blocking EphA4 attenuates motor neuron degeneration in this disease, while too much of it makes the disease worse. EphA4 is a receptor in a system that repels nerves during development and regeneration. Blocking this receptor may therefore be a therapeutic option in ALS. In the current project, we intend to investigate the mechanism through which EphA4 affects ALS. We also will study which substance is the naturally occurring activator of this receptor, and explore whether such ligands can be inactivated. Most importantly, we intend to investigate whether nanobodies against EphA4 can be used as therapeutic agents in ALS. Nanobodies are very simple antibodies that are emerging as very interesting diagnostic and therapeutic tools in medicine. Finally, we will investigate whether compounds that interfere with the signaling cascades that are activated by EphA4, can be of therapeutic value in ALS models. This is of interest as some of these are in clinical use already for the treatment of other diseases.

Date:1 Jan 2014 →  31 Dec 2017
Keywords:Amyotrophic Lateral Sclerosis
Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing