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Equivalent Gene Expression Profiles between Glatopa™ and Copaxone®.

D'Alessandro JS, Duffner J, Pradines J, Capila I, Garofalo K, Kaundinya G, Greenberg BM, Kantor D, Ganguly TC - PLoS ONE (2015)

Bottom Line: Comparative analysis was also performed on sets of transcripts relevant to T-cell biology and antigen presentation, among others that are known to be modulated by glatiramer acetate.No statistically significant differences were observed between Copaxone and Glatopa in the expression levels (magnitude and direction) of these glatiramer acetate-regulated genes.In conclusion, multiple methods consistently supported equivalent gene expression profiles between Copaxone and Glatopa.

View Article: PubMed Central - PubMed

Affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.

ABSTRACT
Glatopa™ is a generic glatiramer acetate recently approved for the treatment of patients with relapsing forms of multiple sclerosis. Gene expression profiling was performed as a means to evaluate equivalence of Glatopa and Copaxone®. Microarray analysis containing 39,429 unique probes across the entire genome was performed in murine glatiramer acetate--responsive Th2-polarized T cells, a test system highly relevant to the biology of glatiramer acetate. A closely related but nonequivalent glatiramoid molecule was used as a control to establish assay sensitivity. Multiple probe-level (Student's t-test) and sample-level (principal component analysis, multidimensional scaling, and hierarchical clustering) statistical analyses were utilized to look for differences in gene expression induced by the test articles. The analyses were conducted across all genes measured, as well as across a subset of genes that were shown to be modulated by Copaxone. The following observations were made across multiple statistical analyses: the expression of numerous genes was significantly changed by treatment with Copaxone when compared against media-only control; gene expression profiles induced by Copaxone and Glatopa were not significantly different; and gene expression profiles induced by Copaxone and the nonequivalent glatiramoid were significantly different, underscoring the sensitivity of the test system and the multiple analysis methods. Comparative analysis was also performed on sets of transcripts relevant to T-cell biology and antigen presentation, among others that are known to be modulated by glatiramer acetate. No statistically significant differences were observed between Copaxone and Glatopa in the expression levels (magnitude and direction) of these glatiramer acetate-regulated genes. In conclusion, multiple methods consistently supported equivalent gene expression profiles between Copaxone and Glatopa.

No MeSH data available.


Related in: MedlinePlus

Box plots for gene expression changes for key Th2 cytokines IL-4 and IL-3 and additional genes related to immune cell function.No statistically significant differences between Glatopa and Copaxone were observed for any of these genes.
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pone.0140299.g007: Box plots for gene expression changes for key Th2 cytokines IL-4 and IL-3 and additional genes related to immune cell function.No statistically significant differences between Glatopa and Copaxone were observed for any of these genes.

Mentions: Two important Th2 cytokines, IL-3 and IL-4, were induced by Copaxone. These changes were similar to those seen with Glatopa (Table 4 and Fig 7). Several key immune cell genes (e.g., FoxP3 and GPR83) reportedly regulated by GA in other biological test systems [29,35] were also examined; Fig 7 shows box plots of seven such specific genes (IFT3, FOXP3, GPR83, CD14, TLR2, CD9, and MMP-14). In the GA-responsive Th2-polarized T-cell test system, the expression of these genes was unchanged (IFT3, FOXP3, GPR83, CD14, and MMP-14) or decreased compared with media-only control. More importantly, no statistically significant differences were observed between the expression levels for any of these genes when Glatopa was compared with Copaxone.


Equivalent Gene Expression Profiles between Glatopa™ and Copaxone®.

D'Alessandro JS, Duffner J, Pradines J, Capila I, Garofalo K, Kaundinya G, Greenberg BM, Kantor D, Ganguly TC - PLoS ONE (2015)

Box plots for gene expression changes for key Th2 cytokines IL-4 and IL-3 and additional genes related to immune cell function.No statistically significant differences between Glatopa and Copaxone were observed for any of these genes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608686&req=5

pone.0140299.g007: Box plots for gene expression changes for key Th2 cytokines IL-4 and IL-3 and additional genes related to immune cell function.No statistically significant differences between Glatopa and Copaxone were observed for any of these genes.
Mentions: Two important Th2 cytokines, IL-3 and IL-4, were induced by Copaxone. These changes were similar to those seen with Glatopa (Table 4 and Fig 7). Several key immune cell genes (e.g., FoxP3 and GPR83) reportedly regulated by GA in other biological test systems [29,35] were also examined; Fig 7 shows box plots of seven such specific genes (IFT3, FOXP3, GPR83, CD14, TLR2, CD9, and MMP-14). In the GA-responsive Th2-polarized T-cell test system, the expression of these genes was unchanged (IFT3, FOXP3, GPR83, CD14, and MMP-14) or decreased compared with media-only control. More importantly, no statistically significant differences were observed between the expression levels for any of these genes when Glatopa was compared with Copaxone.

Bottom Line: Comparative analysis was also performed on sets of transcripts relevant to T-cell biology and antigen presentation, among others that are known to be modulated by glatiramer acetate.No statistically significant differences were observed between Copaxone and Glatopa in the expression levels (magnitude and direction) of these glatiramer acetate-regulated genes.In conclusion, multiple methods consistently supported equivalent gene expression profiles between Copaxone and Glatopa.

View Article: PubMed Central - PubMed

Affiliation: Momenta Pharmaceuticals, Inc., Cambridge, MA, United States of America.

ABSTRACT
Glatopa™ is a generic glatiramer acetate recently approved for the treatment of patients with relapsing forms of multiple sclerosis. Gene expression profiling was performed as a means to evaluate equivalence of Glatopa and Copaxone®. Microarray analysis containing 39,429 unique probes across the entire genome was performed in murine glatiramer acetate--responsive Th2-polarized T cells, a test system highly relevant to the biology of glatiramer acetate. A closely related but nonequivalent glatiramoid molecule was used as a control to establish assay sensitivity. Multiple probe-level (Student's t-test) and sample-level (principal component analysis, multidimensional scaling, and hierarchical clustering) statistical analyses were utilized to look for differences in gene expression induced by the test articles. The analyses were conducted across all genes measured, as well as across a subset of genes that were shown to be modulated by Copaxone. The following observations were made across multiple statistical analyses: the expression of numerous genes was significantly changed by treatment with Copaxone when compared against media-only control; gene expression profiles induced by Copaxone and Glatopa were not significantly different; and gene expression profiles induced by Copaxone and the nonequivalent glatiramoid were significantly different, underscoring the sensitivity of the test system and the multiple analysis methods. Comparative analysis was also performed on sets of transcripts relevant to T-cell biology and antigen presentation, among others that are known to be modulated by glatiramer acetate. No statistically significant differences were observed between Copaxone and Glatopa in the expression levels (magnitude and direction) of these glatiramer acetate-regulated genes. In conclusion, multiple methods consistently supported equivalent gene expression profiles between Copaxone and Glatopa.

No MeSH data available.


Related in: MedlinePlus