Research focus

The peripheral nervous system (PNS) exchanges motor, sensory and autonomic information between the central nervous system (CNS) and the limbs, organs and tissues. A series of biological and environmental conditions, such as genetic mutations, chemical stress, infections or metabolic insults, can lead to axonal loss and demyelination, the pathological hallmarks of peripheral nerve degeneration. Moreover, degeneration of peripheral nerves is accompanied by a local activation of the immune system.

The Peripheral Neuropathy Group aims at understanding the delicate balance between peripheral nerve homeostasis and degeneration by using two paradigms:

  1. How do genetic mutations lead to peripheral nerve degeneration, and

  2. what is the role of the innate immune system in nerve protection?

Inherited peripheral neuropathies (IPN) are caused by a length-dependent degeneration of peripheral nerves, resulting in progressive weakness in the limbs, wasting of foot and hand muscles as well as distal sensory loss. Charcot-Marie-Tooth (CMT) disease is the most common IPN with a prevalence of 1/2500. Over the years, our lab has become one of the main CMT research centers in the world; overall, 1/4 of the 60 IPN disease causing genes were found within our team or via international collaborations. Not surprisingly, many of these genes encode proteins that are involved in myelination and maintenance of the peripheral nerve. However, also ubiquitously expressed genes with basic tasks in every cell were found to specifically cause peripheral nerve degeneration.

Since the identification of a disease-associated gene is only a first step in unraveling the disease pathomechanism, we wanted to go further and aim to understand the functional consequences of the pathogenic mutations. We chose to focus on ubiquitously expressed genes that our lab identified to be causative for CMT. We aim to unravel the unique properties of these proteins in peripheral nerve biology as well as explore how these properties are affected upon mutation. To this end, we developed cellular (sensory and motor neurons or Schwann cells) and animal model systems. We are not only investigating the impact of disease-causing mutations on the well established functions of these proteins, but additionally try to identify novel (potentially neurospecific) pathways in which these proteins might be involved by undertaking large scale approaches. Our ‘gene-driven’ approach is further complemented by a second research line, which aims to identify the role of the innate immune system in neuroprotection and -degeneration. Understanding how this balance is controlled might allow us to fine-tune or even stimulate an inherent neuroprotective response.

We strongly believe that our research strategy can contribute to the development of novel treatment strategies for CMT patients. The on-site interaction between neurologists, molecular geneticists and cell biologists places our lab in a privileged position: it ensures access to patient material, and also allows us to couple back our findings in the lab with clinical data. We also maintain contacts with the International CMT Consortium by co-organising meetings and workshops.