Merck Serono SpA

Guidonia Montecelio, Italy

Merck Serono SpA

Guidonia Montecelio, Italy
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Agency: European Commission | Branch: FP7 | Program: CP-IP | Phase: NMP.2011.1.2-2 | Award Amount: 11.03M | Year: 2012

The objective of the ALEXANDER project is the identification of novel strategies (e.g., proteolytic enzyme strategy, thiomer strategy, zeta potential changing systems, SNEDDS strategy) and the optimization of existing strategies (e.g., disulfide breaking strategy and slippery surface strategy) for the efficient transport of nanocarriers through the mucus gel layer (e.g., intestinal, nasal, ocular, vaginal, buccal, pulmonary). In particular, R&D activities will be focused on the synthesis of functionalized nanocarriers capable of permeating the mucus gel layer and delivering their therapeutic payload to the epithelium. The nanocarriers will be characterized with respect to their physicochemical properties, ability to cross the mucus gel layer, in vitro and in vivo cytotoxicity. The potential of the developed nanocarriers as delivery systems for mucosal administration of macromolecules will be demonstrated via the oral delivery of peptides, oligosaccharides and oligonucleotides and the nasal delivery of a plasmid encoding for an antigen.

PubMed | University of Genoa, Merck KGaA, Endocrinology Unit, Cervello and 6 more.
Type: Journal Article | Journal: Journal of endocrinological investigation | Year: 2016

Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypodNinety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7% of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypodThe easypodThe injection-recording system and other characteristics of easypod

Casarini L.,University of Modena and Reggio Emilia | Lispi M.,Merck Serono S.p.A. | Longobardi S.,Merck Serono S.p.A. | Milosa F.,University of Modena and Reggio Emilia | And 4 more authors.
PLoS ONE | Year: 2012

Human luteinizing hormone (hLH) and chorionic gonadotropin (hCG) act on the same receptor (LHCGR) but it is not known whether they elicit the same cellular and molecular response. This study compares for the first time the activation of cell-signalling pathways and gene expression in response to hLH and hCG. Using recombinant hLH and recombinant hCG we evaluated the kinetics of cAMP production in COS-7 and hGL5 cells permanently expressing LHCGR (COS-7/LHCGR, hGL5/LHCGR), as well as cAMP, ERK1/2, AKT activation and progesterone production in primary human granulosa cells (hGLC). The expression of selected target genes was measured in the presence or absence of ERK- or AKT-pathways inhibitors. In COS-7/LHCGR cells, hCG is 5-fold more potent than hLH (cAMP ED50: 107.1±14.3 pM and 530.0±51.2 pM, respectively). hLH maximal effect was significantly faster (10 minutes by hLH; 1 hour by hCG). In hGLC continuous exposure to equipotent doses of gonadotropins up to 36 hours revealed that intracellular cAMP production is oscillating and significantly higher by hCG versus hLH. Conversely, phospho-ERK1/2 and -AKT activation was more potent and sustained by hLH versus hCG. ERK1/2 and AKT inhibition removed the inhibitory effect on NRG1 (neuregulin) expression by hLH but not by hCG; ERK1/2 inhibition significantly increased hLH- but not hCG-stimulated CYP19A1 (aromatase) expression. We conclude that: i) hCG is more potent on cAMP production, while hLH is more potent on ERK and AKT activation; ii) hGLC respond to equipotent, constant hLH or hCG stimulation with a fluctuating cAMP production and progressive progesterone secretion; and iii) the expression of hLH and hCG target genes partly involves the activation of different pathways depending on the ligand. Therefore, the LHCGR is able to differentiate the activity of hLH and hCG. © 2012 Casarini et al.

Talevi R.,University of Naples Federico II | Barbato V.,University of Naples Federico II | Fiorentino I.,University of Naples Federico II | Braun S.,University of Naples Federico II | And 2 more authors.
Reproductive Biology and Endocrinology | Year: 2013

Background: Spermatozoa are extremely vulnerable to oxidative stress caused by the unbalance between concentrations of reactive oxygen species and antioxidant scavenging systems present inside the male reproductive tract. In spite of a large number of clinical studies that claimed the beneficial effects of antioxidant oral administration on sperm physiology and fertility, only a few studies were addressed to evaluate their effects on spermatozoa in vitro. Main aims of the present study were to assess the influence of zinc, D-aspartate and coenzyme Q10, included in the dietary supplement Genadis (Merck Serono), on human sperm motility, DNA fragmentation and lipid peroxidation.Methods: Semen samples, obtained from forty-four patients (23-30 years of age) were enrolled in this study, twenty-four were normospermic and twenty patients were oligospermic. Semen samples were analysed for sperm progressive motility and kinetics through computer assisted analysis, DNA fragmentation and lipid peroxidation.Results: Main results showed that in both normo and oligospermic samples, total and progressive sperm motility is maintained by in vitro treatment with zinc, D-aspartate and coenzyme Q10, whereas a significant decrease of these parameters occurs in parallel samples incubated in medium alone. Zinc, D-aspartate and coenzyme Q10 also prevented the decrease of sperm kinetics but such an effect was highly significant only in oligospermic samples. Moreover, they also protected spermatozoa by the increase of DNA fragmentation and lipid peroxidation.Conclusions: Zinc, D-aspartate and coenzyme Q10 exert a direct protective effect on human spermatozoa preventing the decrease of motility and the increase of DNA fragmentation and lipid peroxidation during in vitro culture. © 2013 Talevi et al.; licensee BioMed Central Ltd.

Presti C.L.,Merck Serono SpA
Technical Proceedings of the 2011 NSTI Nanotechnology Conference and Expo, NSTI-Nanotech 2011 | Year: 2011

Continuous advances in polymer chemistry are enabling the synthesis of novel responsive biomaterials. This class of biomaterials are polymers able to undergo significant changes in their properties in response to external stimuli. Depending on their chemical architecture, responsive polymers can reversibly or irreversibly vary characteristics such as mechanical properties, appearance, structure, viscosity, volume, electrical conductivity, colour, fluorescence, opacity, shape and, ultimately, function.

Dispenza C.,University of Palermo | Ricca M.,University of Palermo | Lopresti C.,University of Palermo | Lopresti C.,Merck Serono S.p.A. | And 4 more authors.
Polymer Chemistry | Year: 2011

Gelled microemulsions are the subject of considerable scientific and commercial interest. Many efforts are currently devoted to improving their toxicological profile and functioning as biocompatible diffusion barrier for the controlled delivery of hydrophobic compounds. In the present investigation, a non-ionic polymeric surfactant was chosen to generate an oil-in-water microemulsion of a model fragrance in the presence of poly(N-vinyl-2- pyrrolidone) (PVP). The microemulsion was then subjected to either electron-beam or UV-irradiation to induce free-radical crosslinking of PVP at low temperature and in the absence of crosslinking agents, catalysts and initiators. Irradiation conditions with the two irradiation sources have been purposely selected to generate PVP hydrogels with similar appearances and mechanical spectra. Despite the macroscopic analogies, specific features are imparted to the two families of hydrogels by the two different irradiation methodologies. A description of the microstructure of both pure PVP and microemulsion-laden hydrogels is given starting from the dynamic light scattering (DLS) characterization of the liquid (unirradiated) formulations, followed by the study the hydrogels' dynamic mechanical, solubility and swelling properties, FTIR analysis of the water insoluble fractions, DLS measurements and cytotoxicity studies. © The Royal Society of Chemistry.

Behre H.M.,Martin Luther University of Halle Wittenberg | Howles C.M.,ARIES Consulting | Longobardi S.,Merck Serono S.p.A.
Reproductive BioMedicine Online | Year: 2015

In this open-label study, women aged 36-40 years undergoing ovarian stimulation were randomized to recombinant human FSH (rhFSH) plus recombinant human luteinizing hormone (rhLH) from stimulation day 1 (group A; n = 103), or rhFSH alone (days 1-5) followed by rhFSH plus rhLH from day 6 (group B; n = 99). The primary objective was equivalence in number of oocytes retrieved per patient. The mean (±SD) number of oocytes retrieved was 9.7 (±6.9) in group A and 10.9 (±6.5) in group B; the estimated difference between groups (-1.28 oocytes [95% confidence interval: -3.15 to 0.59]) did not reach the predefined limit of equivalence (±3 oocytes). The study's primary objective was therefore not met. In both groups, a mean (±SD) of 1.9 (±0.6) embryos were transferred per patient. Implantation rates were 24.7% in group A and 13.3% in group B. Clinical pregnancy rates per started cycle and per embryo transfer were 31.6% and 34.4% in Group A, 17.2% and 18.9% in Group B. Ovarian hyperstimulation syndrome was reported in four (group A) and five (group B) patients. The potential benefit of initiating LH supplementation earlier during ovarian stimulation in older women is of interest, warranting further exploration. © 2015 The Authors.

La Rocca C.,University of Naples Federico II | La Rocca C.,CNR Institute Experimental Endocrinology and Oncology Gaetano Salvatore | Carbone F.,CNR Institute Experimental Endocrinology and Oncology Gaetano Salvatore | Longobardi S.,Merck Serono S.p.A. | Matarese G.,University of Salerno
Immunology Letters | Year: 2014

Establishment and maintenance of pregnancy represents a challenge for the maternal immune system since it has to defend against pathogens and tolerate paternal alloantigens expressed in fetal tissues. Regulatory T (Treg) cells, a subset of suppressor CD4+ T cells, play a dominant role in the maintenance of immunological self-tolerance by preventing immune and autoimmune responses against self-antigens. Although localized mechanisms contribute to fetal evasion from immune attack, in the last few years it has been observed that Treg cells are essential in promoting fetal survival avoiding the recognition of paternal semi-allogeneic tissues by maternal immune system. Several functional studies have shown that unexplained infertility, miscarriage and pre-clampsia are often associated with deficit in Treg cell number and function while normal pregnancy selectively stimulates the accumulation of maternal forkhead-box-P3+ (FoxP3+) CD4+ Treg cells with fetal specificity. Some papers have been reported that the number of Treg cells persists at elevated levels long after delivery developing an immune regulatory memory against father's antigens, moreover these memory Treg cells rapidly proliferate during subsequent pregnancies, however, on the other hand, there are several evidence suggesting a clear decline of Treg cells number after delivery. Different factors such as cytokines, adipokines, pregnancy hormones and seminal fluid have immunoregulatory activity and influence the success of pregnancy by increasing Treg cell number and activity. The development of strategies capable of modulating immune responses toward fetal antigens through Treg cell manipulation, could have an impact on the induction of tolerance against fetal antigens during immune-mediated recurrent abortion. © 2014 Elsevier B.V.

The present invention concerns the use of a combination consisting of D-aspartic and L-aspartic acids or L-aspartic acid used alone to stimulate the procreative activity in the man by increment of spermatozoon number and motility.

The present invention concerns the use of a combination consisting of D-aspartic and L-aspartic acids or L-aspartic acid used alone to stimulate the procreative activity in the man by increment of spermatozoon number and motility.

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