Homaira Nawabi, Inserm- U1216, Grenoble Institute of Neuroscience, La Tronche, France

Doublecortin peptide mimes to promote CNS axon regeneration

Funded in: 2022, 2023, 2024

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Problem: Need of molecular pathways that are able promote axon regeneration
Target: Doubelcortin seems to be a perfect molecule for treatment
Goal: Find new molecules with therapeutical value

Mature central nervous system (brain and spinal cord) cannot regenerate. Thus, patients suffering from spinal cord injuries must live with permanent disabilities, as complete loss of motor and cognitive functions. Major effort has been done in the past years to identify molecular pathways that are able to promote axon regeneration. However, most of these molecules are not suitable to develop treatment as they lead to cancer development.

Previous work of these neuroscientists identified Doublecortin (DCX), a protein controlling the cytoskeleton as a key mediator of CNS regeneration. Indeed, in mature CNS, overexpression of DCX in the retina, promotes optic nerve regeneration and neuroprotection. Moreover, DCX is not known to control gene expression within cells and is not implicated in cancer. These features make DCX as a perfect molecule to use as a potential drug to treat spinal cord injuries. The neuroscientists have generated a small peptides library derived from DCX. Their results show that some of them exhibit strong growth ability in primary neuronal culture and mature retina explants.

This project proposes to test them in vivo first in the optic nerve. Peptides with the most growth ability in the visual system will be used in spinal cord injuries paradigm. The researchers expect their peptides to promote spinal cord plasticity and/or regeneration and functional recovery. This aims at proposing new molecules with therapeutical value that could be used for spinal cord injury patients to promote axon regeneration and subsequent functional recovery.