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Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin
Published on: March 26, 2015
Remyelination modulators in multiple sclerosis patients
Rabeah Al-Temaimi1, Jehad AbuBaker2, Irina Al-Khairi2
1Human Genetics Unit, Department of Pathology, Faculty of Medicine, Kuwait University, Jabriya, Kuwait.
Abstract:
Multiple Sclerosis (MS) is a complex autoimmune neuro-inflammatory disorder characterized by persistent MS plaques in the central nervous system. Resolution of MS plaques is dependent on the remyelination competence of surviving oligodendrocytes and surrounding environment. Here, we assessed myelination modulators in a 100 MS patients against 77 healthy controls. Plasma fractions were used for the assessment of insulin growth factor binding protein1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) using a Luminex multiplex assay, whereas neurofilament light chain (NF-L) was assessed with an enzyme-linked immunosorbent assay. Circulating levels of IGFBP1, LCN2 and NF-L were significantly higher in MS patients (p<0.01). Whereas BDNF levels were significantly lower in MS patients (p=0.014). MS Female patients had significantly higher levels of IGFBP1 compared to male MS patients (p=0.006). MS patients treated with fingolimod had higher LCN2 levels compared to those on natalizumab (r=0.25, p=0.03). Higher NF-L levels associated with clinically isolated syndrome's (CIS) conversion into MS (p=0.002). We conclude that low BDNF and high LCN2 and NF-L levels are associated with MS pathogenesis, and high IGFBP1level is a biomarker for female MS only, suggesting different MS progression pathways between the sexes. LCN2 is a candidate predictor of response to natalizumab treatment, and NF-L is a candidate predictor of CIS conversion into MS.
Insights
This study found that lower brain-derived neurotrophic factor (BDNF) and higher lipocalin2 (LCN2) and neurofilament light chain (NF-L) are linked to Multiple Sclerosis (MS) development. Insulin growth factor binding protein 1 (IGFBP1) may indicate MS in females.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Autoimmune Disorders
Background:
- Multiple Sclerosis (MS) is a neuro-inflammatory disease impacting the central nervous system.
- Remyelination is crucial for MS plaque resolution, influenced by oligodendrocytes and the microenvironment.
- Understanding myelination modulators is key to MS pathogenesis and treatment.
Purpose of the Study:
- To investigate circulating levels of myelination modulators in Multiple Sclerosis (MS) patients.
- To identify potential biomarkers for MS, disease progression, and treatment response.
- To explore sex-specific differences in MS-related biomarker levels.
Main Methods:
- Assessed plasma levels of insulin growth factor binding protein 1 (IGFBP1), brain-derived neurotrophic factor (BDNF), and lipocalin2 (LCN2) in 100 MS patients and 77 healthy controls using Luminex multiplex assay.
- Measured neurofilament light chain (NF-L) levels via enzyme-linked immunosorbent assay.
- Correlated biomarker levels with clinical data, including sex, treatment, and conversion from clinically isolated syndrome (CIS) to MS.
Main Results:
- MS patients exhibited significantly higher IGFBP1, LCN2, and NF-L levels, and lower BDNF levels compared to controls.
- Elevated IGFBP1 levels were observed specifically in female MS patients.
- Higher LCN2 levels were found in MS patients treated with fingolimod versus natalizumab; higher NF-L levels predicted CIS conversion to MS.
Conclusions:
- Low BDNF and elevated LCN2 and NF-L are associated with MS pathogenesis.
- High IGFBP1 may serve as a female-specific MS biomarker, suggesting sex-based differences in disease progression.
- LCN2 and NF-L show potential as predictors for natalizumab treatment response and CIS conversion to MS, respectively.

