Identification of a therapeutic strategy to reduce fibrotic scarring and promote central nervous system repair.

Damage to the adult mammalian central nervous system (CNS) often leads to persistent functional deficits.

The establishment of these deficits is associated with scar tissue that forms locally at lesions, blocking regeneration.

We previously identified fibrotic scarring by a specific subset of perivascular cells as a new therapeutic target to promote recovery following CNS injury. In our current VR project, we discovered that fibrotic scarring is triggered by myelin damage.

White matter lesions cause more fibrotic scarring compared to grey matter lesions, establishing an unexpected heterogeneity of CNS scars.

We consequently identified the myelin-associated axon growth inhibitors Nogo, OMgp and MAG, as key fibrosis-inducing factors.I propose to further investigate the molecular mechanisms of myelin damage-induced fibrosis with the aim to identify agents to modulate scarring.

We will test different translational strategies to either block Nogo, OMgp and MAG or interfere with their common receptor binding.

Using single cell expression profiling, we will determine relevant activation stages and differentiation steps leading to fibrotic scar tissue formation.

Finally, we will use our combined knowledge to design and test therapeutic strategies to attenuate fibrotic scarring and improve recovery after spinal cord injury.