Investigations

In multiple sclerosis, an “energy crisis”, which entails axonal ATP depletion, contributes to neuronal dysfunction and ensuing neurodegeneration. We have identified dysregulation of the TCA cycle and specifically depletion of its pacemaker enzyme, IDH3, as a critical checkpoint of neuronal energy homeostasis. Targeting IDH3, however, leads only to partial reversal of axonal ATP deficits, pointing to further neuroenergetic checkpoints. We now plan to identify these checkpoints and study their ...

In demyelinating CNS diseases, remyelination is mostly driven by newly differentiating oligodendrocytes (OLs) but often remains insufficient. Our recent work shows that surviving OLs can contribute to myelin repair both in animal models of multiple sclerosis and in patients, although this contribution is often inefficient. We believe that surviving OLs can be recruited to the remyelination process if we target the molecular checkpoints determining their repair capacity in the inflamed CNS. ...