Impact of glatiramer acetate on paraclinical markers of neuroprotection in multiple sclerosis: A prospective observational clinical trial

J Neuroimmunol. 2015 Oct 15:287:98-105. doi: 10.1016/j.jneuroim.2015.08.004. Epub 2015 Aug 10.

Abstract

Data from in vitro and animal studies support a neuroprotective role of glatiramer acetate (GA) in multiple sclerosis (MS). We investigated prospectively whether treatment with GA leads to clinical and paraclinical changes associated with neuroprotection in patients with relapsing-remitting (RR) MS. Primary aim of this clinical study was to determine serum BDNF levels in RR-MS patients who were started on GA as compared to patients who remained therapy-naive throughout 24 months. Secondary outcomes included relapses and EDSS, cognition, quality of life, fatigue and depression, BDNF expression levels on peripheral immune cells (FACS, RT-PCR), serum anti-myelin basic peptide (MBP) antibody status, evoked potential and cerebral MRI studies. While GA treatment did not alter serum levels or expression levels on peripheral immune cells of BDNF over time it resulted in a transient increase of serum IgG antibody response to MBP, mainly due to subtype IgG1 (p<0.05), after 3 months. However, no significant differences were found between GA treated and therapy-naive patients with regard to serum BDNF and intracellular BDNF expression levels, nerve conduction (including median and tibial nerve somatosensory, pattern-shift visual and upper and lower limb motor evoked potentials) or MRI (including volume of hyperintense lesions, volume of hypointense lesions after CE, mean diffusivity and fractional anisotropy) outcome parameters. In conclusion, our findings do not support a major impact of GA treatment on paraclinical markers of neuroprotection in human RR-MS.

Keywords: Brain derived neurotrophic factor (BDNF); Glatiramer acetate (GA); Multiple sclerosis (MS); Neuroprotection.

Publication types

  • Clinical Trial
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Antibodies / metabolism
  • Brain-Derived Neurotrophic Factor / blood
  • Brain-Derived Neurotrophic Factor / genetics
  • Cerebral Cortex / pathology
  • Disability Evaluation
  • Electroencephalography
  • Evoked Potentials / drug effects
  • Female
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / drug therapy*
  • Myelin Basic Protein / immunology
  • Neuropsychological Tests
  • RNA, Messenger / metabolism
  • Time Factors
  • Treatment Outcome*

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Brain-Derived Neurotrophic Factor
  • Myelin Basic Protein
  • RNA, Messenger
  • Glatiramer Acetate