Natalizumab treatment associated with reduction of gliotic biomarkers in white matter

EAN 2019

Natalizumab treatment associated with reduction of gliotic biomarkers in white matter

3067 2300 Michael Furrer, PhD

New data on the effect of natalizumab treatment on neuronal and membrane integrity in lesional white matter were presented at the recent 5th Annual Congress of the European Academy of Neurology (EAN) in Oslo, Norway.1

Natalizumab, a humanised monoclonal antibody against the cell adhesion molecule α4-integrin, is an efficacious therapy in treating patients with relapsing-remitting MS (RRMS). Natalizumab has been shown to improve clinical, radiological and patient-reported measures of disease activity.2-5

In the presented study, the effect of natalizumab treatment over 48 months on metabolites of neuronal and membrane integrity was assessed by magnetic resonance spectroscopy in lesional white matter of RRMS patients and normal-appearing white matter of healthy control subjects. The study included eight patients who switched to natalizumab treatment from either interferon (IFN) or glatiramer acetate (GA), 10 patients who continued the IFN/GA regimen and 10 healthy controls.

Schoonheim et al. were able to show a significant decrease of myo-inositol levels by 25.5% (P=0.033) in lesional white matter of patients treated with natalizumab, whereas patients on continuous IFN/GA treatment only showed a reduction of 11.9% (P=0.084). Myo-inositol is a biomarker of gliotic activity and gliosis, i.e. reactive changes of glial cells in response to damage to the central nervous system.6,7 In accordance with this, myo-inositol and levels of other biomarkers were significantly higher in the two patient groups compared to the healthy control subjects at baseline. In contrast to earlier studies, metabolite levels were normalised to creatinine – a metabolic biomarker of both neurons and glial cells that is thought to remain unaffected by MS disease processes. Taken together, the reduction in myo-inositol levels in lesional white matter of RRMS patients may indicate preservation of tissue integrity associated with natalizumab treatment.


References:

  1. Schoonheim MM, et al. Long-term natalizumab treatment is associated with a reduction in lesional white matter levels of myo-inositol, a biomarker of gliotic activity. Presented at the European Academy of Neurology – 5th Congress (2019), June 29 – July 2, 2019, Oslo, Norway.
  2. Sastre-Garriga J, et al. Brain atrophy in natalizumab-treated patients: A 3-year follow-up. Mult Scler. 2015;21:749-756.
  3. Foley JF, et al. Long-term natalizumab treatment is associated with sustained improvements in quality of life in patients with multiple sclerosis. Patient Prefer Adherence. 2017;11:1035-1048.
  4. Miller DH, et al. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurol. 2007;68:1390-1401.
  5. Havrdova E, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. 2009;8:254-260.
  6. Bitsch A, et al. Inflammatory CNS demyelination: histopathologic correlation with in vivo quantitative proton MR spectroscopy. Am J Neuroradiol. 1999;20:1619-1627.
  7. Narayana PA. Magnetic resonance spectroscopy in the monitoring of multiple sclerosis. J Neuroimaging. 2005;15:46S-57S.
Brainwork is supported by unrestricted grants from: