Differential Transcription of SOCS5 and SOCS7 in Multiple Sclerosis Patients Treated with Interferon Beta or Glatiramer Acetate.

The participation of proinflammatory cytokines in the progression of Multiple Sclerosis (MS) has been well documented. Cytokines activate the JAK-STAT pathway, in which the suppressors of cytokine signaling (SOCS) exert a negative feedback. This paper analyzes the levels of SOCS5 and SOCS7 transcripts, quantified by RT-qPCR, in MS patients, and the concentrations of proinflammatory cytokines, IFN-γ, IL17, and IL6, determined by ELISA. Samples of peripheral blood were obtained from MS patients in the relapsing-remitting phase, treated with IFN-ß or glatiramer acetate (GA), and from healthy individuals. SOCS7 mRNA was significantly higher in patients treated with GA (1.36 ± 0.23) than in those treated with IFN-ß (0.65 ± 0.1). Regarding gender, the level of SOCS5 and SOCS7 transcripts were similar between MS and healthy females; in MS males, the level of SOCS7 transcripts were significantly lower (0.59 ± 0.03) than in healthy males (1.008 ± 0.05). Plasmatic levels of IFN-γ were significantly higher in MS patients (60 pg/mL, range 0-160) than in healthy subjects (0 range, 0-106). The same pattern was observed in MS patients treated with IFN-ß (68 pg/mL, range 0-160) compared to patients treated with GA (51 pg/mL, range 0-114), and in MS females (64 pg/mL, range 0-161) compared to healthy females (0, range 0-99). We hypothesize that the increase in SOCS7 transcription in patients treated with GA could partially explain the action mechanism of this drug, while the increase in the concentration of IFN-γ in MS patients could help elucidate the immunopathology of the disease.

Biological and nonbiological complex drugs for multiple sclerosis in Latin America: regulations and risk management.

Biological drugs and nonbiological complex drugs with expired patents are followed by biosimilars and follow-on drugs that are supposedly similar and comparable with the reference product in terms of quality, safety and efficacy. Unlike simple molecules that can be copied and reproduced, biosimilars and follow-on complex drugs are heterogeneous and need specific regulations from health and pharmacovigilance agencies. A panel of 14 Latin American experts on multiple sclerosis from nine different countries met to discuss the recommendations regarding biosimilars and follow-on complex drugs for treating multiple sclerosis. Specific measures relating to manufacturing, therapeutic equivalence assessment and pharmacovigilance reports need to be implemented before commercialization. Physical, chemical, biological and immunogenic characterizations of the new product need to be available before clinical trials start. The new product must maintain the same immunogenicity as the original. Automatic substitution of biological and complex drugs poses unacceptable risks to the patient.

Quantitative analysis of the suppressors of cytokine signaling 1 and 3 in peripheral blood leukocytes of patients with multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by a triad of inflammation, demyelination and gliosis. Because the suppressors of cytokine signaling (Socs) regulate the immune response, we quantified SOCS1 and SOCS3 transcription in peripheral blood leukocytes of patients with MS. SOCS1 transcription decreased significantly in MS patients compared with neurologically healthy persons (0.08±0.02 vs. 1.02±0.23; p=0.0001); while SOCS3 transcription increased in MS patients compared with controls (2.76±0.66 vs. 1.03±0.27; p=0.0008). Our results showed an imbalance of SOCS1 and SOCS3 transcription in MS patients, and a moderated negative correlation between them (Spearman's r=-0.57; p=0.0003).

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents.

OBJECTIVE: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. METHODS: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. RESULTS: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. CONCLUSIONS: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents / Algoritmo latino-americano para tratamento da esclerose múltipla remitente-recorrente utilizando drogas modificadoras da doença

OBJECTIVE: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. METHODS: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. RESULTS: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. CONCLUSIONS: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

OBJETIVO: Estima-se que haja aproximadamente 50.000 pessoas com a forma remitente-recorrente da esclerose múltipla na América Latina. Os algoritmos de tratamento norte-americanos e europeus não levam em consideração nossas peculiaridades regionais, nem a dificuldade no acesso ao tratamento por parte dos pacientes. MÉTODOS: O Fórum Latino-americano de Esclerose Múltipla é um grupo de especialistas independente e suprainstitucional, que avaliou as mais recentes evidências científicas sobre a eficácia e a segurança das drogas modificadoras do curso da doença. Foram avaliados também o acesso ao tratamento e os programas de farmacovigilância de cada um dos oito países representados no Fórum. RESULTADOS: Uma lista específica de recomendações baseadas em evidências científicas foi estabelecida para a América Latina. Também foram discutidas perspectivas de futuros tratamentos para esclerose múltipla. CONCLUSÕES: O presente estudo representou um esforço dos representantes de oito países latino-americanos em discutir um assunto que não pode ser adaptado para uso em nossa região diretamente a partir de recomendações de tratamento europeias ou norte-americanas.