Limits...
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

MDS plots based on the 4176 Copaxone-responsive probes.As expected, clear separation is obtained between Copaxone and media groups. There is also clear separation between media and copolymer groups (ACN, Copaxone, or Glatopa), some separation between GA (Copaxone or Glatopa) and ACN and no visible separation between Copaxone and Glatopa. ACN, acetonitrile nonconforming copolymer; GA, glatiramer acetate; MDS, multidimensional scaling.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4608686&req=5

pone.0140299.g003: MDS plots based on the 4176 Copaxone-responsive probes.As expected, clear separation is obtained between Copaxone and media groups. There is also clear separation between media and copolymer groups (ACN, Copaxone, or Glatopa), some separation between GA (Copaxone or Glatopa) and ACN and no visible separation between Copaxone and Glatopa. ACN, acetonitrile nonconforming copolymer; GA, glatiramer acetate; MDS, multidimensional scaling.

Mentions: The results presented in Table 3, which are based on multivariate statistic t, corroborated results of Table 2. Based on permutation testing, which preserves gene coexpression, Table 3 showed a significant difference between Glatopa and media, a significant difference between ACN and media, a significant difference between GA (Copaxone or Glatopa) and ACN, and no significant difference between Copaxone and Glatopa (P = 0.5). The MDS plot (Fig 3) provides a visual illustration of these conclusions based on the 4176 Copaxone-responsive probes. There is clear separation between media and the three other groups (ACN, Glatopa, and Copaxone) and separation between ACN and GA (Copaxone or Glatopa), but there is no meaningful separation between Copaxone and Glatopa.


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)

MDS plots based on the 4176 Copaxone-responsive probes.As expected, clear separation is obtained between Copaxone and media groups. There is also clear separation between media and copolymer groups (ACN, Copaxone, or Glatopa), some separation between GA (Copaxone or Glatopa) and ACN and no visible separation between Copaxone and Glatopa. ACN, acetonitrile nonconforming copolymer; GA, glatiramer acetate; MDS, multidimensional scaling.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0140299.g003: MDS plots based on the 4176 Copaxone-responsive probes.As expected, clear separation is obtained between Copaxone and media groups. There is also clear separation between media and copolymer groups (ACN, Copaxone, or Glatopa), some separation between GA (Copaxone or Glatopa) and ACN and no visible separation between Copaxone and Glatopa. ACN, acetonitrile nonconforming copolymer; GA, glatiramer acetate; MDS, multidimensional scaling.
Mentions: The results presented in Table 3, which are based on multivariate statistic t, corroborated results of Table 2. Based on permutation testing, which preserves gene coexpression, Table 3 showed a significant difference between Glatopa and media, a significant difference between ACN and media, a significant difference between GA (Copaxone or Glatopa) and ACN, and no significant difference between Copaxone and Glatopa (P = 0.5). The MDS plot (Fig 3) provides a visual illustration of these conclusions based on the 4176 Copaxone-responsive probes. There is clear separation between media and the three other groups (ACN, Glatopa, and Copaxone) and separation between ACN and GA (Copaxone or Glatopa), but there is no meaningful separation between Copaxone and Glatopa.

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