Contributions
Abstract: EP1310
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Natalizumab treatment in pediatric multiple sclerosis (MS) population has a good efficacy reducing relapse rate and disability progression. However, the effect of Natalizumab on children puberty and development is not fully covered.
Objective: To determine whether Natalizumab treatment affects the expression of age, gender and Tanner developmental stage related genes.
Methods: Peripheral blood mononuclear cells (PBMC) were obtained from pediatric MS patients at baseline and at one year of Natalizumab treatment. Gene expression microarray analysis using Affymetrix Inc. technology (HU-133A-2 microarrays) was performed. Transcriptional changes associated with Natalizumab treatment and patients´ age, gender and Tanner developmental stages were analyzed by weighted gene co-expression network analysis (WGCNA) software. This method creates clusters of highly correlated genes which can be related to treatment and children developmental external traits. Biological functional analysis was performed by Ingenuity software.
Results: Gene expression data of 10 pediatric MS patients, 6 females, age 13.9±0.6 years, disease duration 1.5±0.3 years and Tanner scale measurements ranging from pre-adolescent to fully mature morphology, demonstrated a network of 722 coordinately changing genes organized in 3 WGCNA modules induced by Natalizumab treatment (p< 0.05). This signature was associated with differentiation of pre-B-Cells (p=3.05E-09) and B-Cells (5.34E-07), proliferation (p=4.23E-06) and expansion (p=1.04E-04) of B-Cells, similarly to Natalizumab molecular effects in adult MS patients. Age, gender and Tanner stage were associated with two modules each, all distinct from Natalizumab-induced modules. No significant correlations were found between Natalizumab induced gene-modules and age, gender and Tanner stage related traits.
Conclusion: Natalizumab treatment in pediatric MS population does not affect pubertal and developmental genes.
Disclosure:
Achiron Anat: Consulting fees: (EMD Serono, Genzyme, Roche); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Menascu S: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Dolev M: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Magalashvili D: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Michael Gurevich: contracted research (Biogen Idec, Teva, Merck)
Robinson Bracha: nothing to disclose
Abstract: EP1310
Type: ePoster
Abstract Category: Clinical aspects of MS - 3 Paediatric MS
Background: Natalizumab treatment in pediatric multiple sclerosis (MS) population has a good efficacy reducing relapse rate and disability progression. However, the effect of Natalizumab on children puberty and development is not fully covered.
Objective: To determine whether Natalizumab treatment affects the expression of age, gender and Tanner developmental stage related genes.
Methods: Peripheral blood mononuclear cells (PBMC) were obtained from pediatric MS patients at baseline and at one year of Natalizumab treatment. Gene expression microarray analysis using Affymetrix Inc. technology (HU-133A-2 microarrays) was performed. Transcriptional changes associated with Natalizumab treatment and patients´ age, gender and Tanner developmental stages were analyzed by weighted gene co-expression network analysis (WGCNA) software. This method creates clusters of highly correlated genes which can be related to treatment and children developmental external traits. Biological functional analysis was performed by Ingenuity software.
Results: Gene expression data of 10 pediatric MS patients, 6 females, age 13.9±0.6 years, disease duration 1.5±0.3 years and Tanner scale measurements ranging from pre-adolescent to fully mature morphology, demonstrated a network of 722 coordinately changing genes organized in 3 WGCNA modules induced by Natalizumab treatment (p< 0.05). This signature was associated with differentiation of pre-B-Cells (p=3.05E-09) and B-Cells (5.34E-07), proliferation (p=4.23E-06) and expansion (p=1.04E-04) of B-Cells, similarly to Natalizumab molecular effects in adult MS patients. Age, gender and Tanner stage were associated with two modules each, all distinct from Natalizumab-induced modules. No significant correlations were found between Natalizumab induced gene-modules and age, gender and Tanner stage related traits.
Conclusion: Natalizumab treatment in pediatric MS population does not affect pubertal and developmental genes.
Disclosure:
Achiron Anat: Consulting fees: (EMD Serono, Genzyme, Roche); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Menascu S: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Dolev M: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Magalashvili D: Consulting fees: (Genzyme); contracted research (Bayer, Biogen Idec, EMD Serono, Genzyme, Roche).
Michael Gurevich: contracted research (Biogen Idec, Teva, Merck)
Robinson Bracha: nothing to disclose