Long-term effectiveness of glatiramer acetate in clinical practice conditions.

Glatiramer acetate currently represents one of the main treatments for relapsing-remitting multiple sclerosis (RRMS). However, the information available about its long-term effect in clinical practice is still limited. Thus, this multicenter retrospective cohort study aimed to assess the long-term effectiveness of glatiramer acetate in this setting. The study population included RRMS patients treated with glatiramer acetate for at least 5 years after its marketing authorization and the primary endpoint was long-term clinical effectiveness, defined as absence of disability progression for at least five consecutive years. A total of 149 patients were included into the study, who had received glatiramer acetate for a mean of 6.9 ± 1.4 years (5 years, n=149; 6 years, n=112; 7 years, n=63; 8 years, n=32; 9 years, n=21). More than 85% of patients remained free from disability progression through years 1 to 9 of glatiramer acetate treatment, and 75.2% showed absence of disability progression for at least five consecutive years. Expanded Disability Status Scale (EDSS) scores were maintained, with most patients showing stable/improved EDSS and 92.6% sustaining EDSS <6. Decreased annual relapse rates and increased proportion of relapse-free patients were maintained during the whole glatiramer acetate treatment compared to the year prior to its authorization (p<0.001). The number of gadolinium-enhanced T1-weighted lesions also decreased from pre-glatiramer-acetate assessment to last follow-up whilst on glatiramer acetate (p<0.05). In conclusion, administration of glatiramer acetate shows long-term clinical effectiveness for RRMS treatment; its effect under clinical practice conditions slowed disability progression and reduced relapse occurrence for up to 9 years.

A study on the mechanisms by which minocycline protects against MDMA ('ecstasy')-induced neurotoxicity of 5-HT cortical neurons.

3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') is a selective 5-HT neurotoxin in rat brain which has been shown to produce acute neuroinflammation characterized by activation of microglia and release of interleukin-1beta (IL-1beta). We aimed to determine whether or not minocycline, a semi-synthetic tetracycline antibiotic capable of inhibiting microglial activation, could prevent the inflammatory response and reduce the toxicity induced by MDMA. Adult male Dark Agouti rats were given minocycline twice a day for 2 days (45 mg/kg on the first day and 90 mg/kg on the second day; 12-h apart, i.p.). MDMA (12.5 mg/kg; i.p.) was given after the third minocycline injection and animals were killed either 1 h later for the determination of NFkappaB binding activity, 3 h later for the determination of IL-1beta, 24 h later for the determination of microglial activation or 7 days later for the determination of [(3)H]-paroxetine binding as a measure of 5-HT neurotoxicity. MDMA increased NFkappaB activation, IL-1beta release and microglial activation both in the frontal cortex and in the hypothalamus and 7 days later produced a reduction in the density of 5-HT uptake sites in both these brain areas. Minocycline prevented the MDMA-induced increase in NFkappaB activation, IL-1beta release and microglial activation in the frontal cortex and prevented the 5-HT neurotoxicity 7 days later. However, in the hypothalamus, in spite of preventing MDMA-induced microglial activation, minocycline failed to prevent MDMA-induced NFkappaB activation, IL-1beta release and neurotoxicity. This suggests that the protective mechanism of minocycline against MDMA-induced neurotoxicity in frontal cortex involves inhibition of MDMA-induced NFkappaB activation possibly through a reduction in IL-1beta signalling.