Pharmacogenomics of Interferon-ß Therapy in Multiple Sclerosis: Baseline IFN Signature Determines Pharmacological Differences between Patients

Multiple sclerosis (MS) is a heterogeneous disease. In order to understand the partial responsiveness to IFNbeta in Relapsing Remitting MS (RRMS) we studied the pharmacological effects of IFNbeta therapy. Large scale gene expression profiling was performed on peripheral blood of 16 RRMS patients at baseline and one month after the start of IFNbeta therapy. Differential gene expression was analyzed by Significance Analysis of Microarrays. Subsequent expression analyses on specific genes were performed after three and six months of treatment. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated in vitro with IFNbeta. Genes of interest were measured and validated by quantitative realtime PCR. An independent group of 30 RRMS patients was used for validation. Pharmacogenomics revealed a marked variation in the pharmacological response to IFNbeta between patients. A total of 126 genes were upregulated in a subset of patients whereas in other patients these genes were downregulated or unchanged after one month of IFNbeta therapy. Most interestingly, we observed that the extent of the pharmacological response correlates negatively with the baseline expression of a specific set of 15 IFN response genes (R = -0.7208; p = 0.0016). The negative correlation was maintained after three (R = -0.7363; p = 0.0027) and six (R = -0.8154; p = 0.0004) months of treatment, as determined by gene expression levels of the most significant correlating gene. Similar results were obtained in an independent group of patients (n = 30; R = -0.4719; p = 0.0085). Moreover, the ex vivo results could be confirmed by in vitro stimulation of purified PBMCs at baseline with IFNbeta indicating that differential responsiveness to IFNbeta is an intrinsic feature of peripheral blood cells at baseline. These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNbet

Crescent MOONS: an update on the ongoing construction of the new VLT's multi-object spectrograph

International audienceThe Multi Object Optical and Near-infrared Spectrograph (MOONS) instrument is the next generation multi-object spectrograph for the VLT. This powerful instrument will combine for the first time: the large collecting power of the VLT with a high multipexing capability offered by 1000 optical fibres moved with individual robotic positioners and a novel, very fast spectrograph able to provide both low- and high-resolution spectroscopy simultaneously across the wavelength range 0.64μm - 1.8μm. Such a facility will provide the astronomical community with a powerful, world-leading instrument able to serve a wide range of Galactic, Extragalactic and Cosmological studies. Th final assembly, integration and verification phase of the instrument is now about to start performance testing

Rising MOONS: an update on the VLT's next multi-object spectrograph as it begins to grow

International audienceAfter completion of its final-design review last year, it is full steam ahead for the construction of the MOONS instrument - the next generation multi-object spectrograph for the VLT. This remarkable instrument will combine for the first time: the 8 m collecting power of the VLT, 1000 optical fibres with individual robotic positioners and both medium- and high-resolution spectral coverage acreoss the wavelength range 0.65μm - 1.8 μm. Such a facility will allow a veritable host of Galactic, Extragalactic and Cosmological questions to be addressed. In this paper we will report on the current status of the instrument, details of the early testing of key components and the major milestones towards its delivery to the telescope

HARMONI at ELT: overview of the capabilities and expected performance of the ELT's first light, adaptive optics assisted integral field spectrograph.

International audienc

MOONS: The New Multi-Object Spectrograph for the VLT

International audienceMOONS is the new Multi-Object Optical and Near-infrared Spectrograph currently under construction for the Very Large Telescope (VLT) at ESO. This remarkable instrument combines, for the first time, the collecting power of an 8-m telescope, 1000 fibres with individual robotic positioners, and both low- and high-resolution simultaneous spectral coverage across the 0.64–1.8 μm wavelength range. This facility will provide the astronomical community with a powerful, world-leading instrument able to serve a wide range of Galactic, extragalactic and cosmological studies. Construction is now proceeding full steam ahead and this overview article presents some of the science goals and the technical description of the MOONS instrument. More detailed information on the MOONS surveys is provided in the other dedicated articles in this Messenger issue