Gene expression analysis reveals functional pathways of glatiramer acetate activation

Abstract

GA-induced functional pathways coincide with known mechanisms of GA activity in MS patients and further support the unique therapeutic effect of this drug.

B Cell Receptor Recognition of Glatiramer Acetate is Required for Efficacy through Antigen Presentation and Cytokine Production

“…It is important to note that GA also bound to a small percentage of monocytes (5-15%) and CD4 + T cells (3-10%) but very few, if any, CD8 + T cells or natural killer cells (data not shown). This binding data supports others work showing effects of GA on various immune cell populations [25,27,28,31,36,37,39]. An interesting finding is that a shift in the negative population not observed with the fluorochrome alone, termed GA lo , was observed when B lymphocytes were incubated with GA ( Figures 1A and 1C).…”

Glatiramoids

“…Although common nonspecific analytical methods can indicate similarities between Copaxone ® and purported generic GA products, they also identify important differences in physicochemical properties, including mixture composition, polypeptide sizes, and charge distribution. Similarly, gene expression studies show profoundly different gene transcription profiles from GA-activated mouse splenocytes when re-activated ex vivo with GA, from transcription profiles when splenocytes are re-activated with purported generic GA product (Bakshi et al 2013;Towfic et al 2014;Citizens petition 2013Citizens petition , 2014. Moreover, gene expression analysis has shown that at least one purported generic GA product (Glatimer ® ) with multiple different marketed batches ( N > 10) demonstrates very poor batch-to-batch consistency of biological effects (Bakshi et al 2013;Nicholas 2012;Towfic et al 2014;Citizen Petition 2009).…”

“…However, important differences from Copaxone ® have been detected using sophisticated state-of-the-art technologies (Bakshi et al 2013;Towfic et al 2014). As described here, information gleaned by comparing Copaxone ® with some of the purported generic GA products is contributing to a better understanding of the complexity of glatiramoids, and of the crucial relationship between drug manufacture and drug identity and quality for members of the glatiramoid class furthermore, the biological and clinical implications of lack of sameness have been examplified in Teva's multiple publications and citizen petitions.…”

Non-biological complex drugs and their analogues in the pathogenetic therapy of multiple sclerosis: Issues of efficacy and safety in clinical use

“…Соот-ветственно, проведение фармакокинетических исследо-ваний для установления биоэквивалентности ГА-подоб-ных препаратов с оригинальным препаратом (Копак-сон ® -Тева) не представляется возможным. До настояще-го времени не выявлены валидированные биомаркеры для оценки эффективности препарата [15]. Копаксон ® -Тева был создан в ходе экспериментов, в которых изучали действие различных антигенов, применяе-мых для воспроизводства экспериментального аутоиммун-ного энцефалита (ЭАЭ) у мышей в Институте имени Вейц-мана (Реховот, Израиль).…”

“…Поскольку биомаркеры ответа и маркеры фармакоди-намики ГА до сих пор не разработаны [15], трудно провести его сравнение с другими глатирамоидами. Ряд авторов раз-работали инновационные расчетные методы, которые могут надежно охарактеризовать различия иммунологического воздействия ГА и ГА-подобных препаратов.…”