Multiple Sclerosis and related disorders

Staff

Jacques De Keyser
Marie D’hooghe
Guy Nagels
Ron Kooijman
Miguel D’haeseleer

Pre-doc

Melissa Cambron
Stephanie Hostenbach
Tatjana Reynders

Technical/administrative Support

Anke De Smedt  (laboratory technician)
Annick Van Meirhaegen-Wieleman (MS nurse)


The role of astrocytes  

Several lines of evidence point to a dysfunction of astrocytes, which are involved in controlling immune responses, energy metabolism and perfusion of the CNS.
Key findings in astrocytes of MS patients:

  • downregulation of  beta2 adrenergic receptors [supposed to play a role in facilitating immune responses, reduced axonal energy metabolism, and reduced trophic support (BDNF)]
  • reduced PCr metabolism due to reduced brain creatine kinase (CK-B) levels (might be involved in reduced glutamate uptake and excitotoxicity)
  • increased expression of endothelin-1 in reactive astrocytes in MS plaques (likely responsible for the decreased cerebral perfusion in MS)

Pathophysiological mechanisms related to these findings are studies in cell cultures, postmortem MS brain samples, microdialysis in small rodents and genetic mouse models (e.g. astrocyte selective beta2 AR KO mouse), MR spectroscopy and perfusion studies in patients with MS.
Findings are further evaluated in proof-of-concept studies, which may lead to clinical trials with new therapeutic approaches. A current study evaluates the effect of fluoxetine and prucalopride in CNS energy metabolism and perfusion (CAME study). A clinical trial using fluoxetine (FLUOX-PMS) in progressive MS is ongoing.
New studies will target the endothelin-1 system with the aim of improving CBF in patients with MS.


Factors that influence the disease course

By investigating factors that influence the course of the disease we intend to find
clues of pathophysiological mechanisms that protect MS patients against new lesion formation and the axonal degeneration responsible for the progressive phase. Interesting findings are further investigated in proof-of concept studies in animal models of MS and patients with MS. A new area of interest that is being studied is the role of the gut microbioma and balance of the autonomic nervous system in MS.


Cognition

See Cognition and Modelling

 

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