Covadonga Pañeda

Scripps Research Institute

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Tamara Martı́nez

Universidad Católica Nuestra Señora de la Asunción

Verónica Ruz

Ophthalmology Associates (United States)

Ana I. Jiménez

Hospital Arnau de Vilanova

Victoria González

Université de Montpellier

Isabel Varela‐Nieto

Hospital La Paz Institute for Health Research

Laura M. Frago

Hospital Infantil Universitario Niño Jesús

Ana Isabel Jiménez

Hospital Universitario Puerto Real

Julie A. Chowen

IMDEA Food

Beatriz Vargas

Universidade Estadual de Campinas (UNICAMP)

Jesús Argente

Universidad Autónoma de Madrid

Cooperative Institutions

Instituto de Salud Carlos III

Consejo Superior de Investigaciones Científicas

Scripps Research Institute

Universidad Autónoma de Madrid

Centro de Investigación Biomédica en Red

Universitat de Barcelona

Instituto de Investigaciones Biomédicas Sols-Morreale

Menéndez Pelayo International University

Universidad de Valladolid

Hospital Infantil Universitario Niño Jesús

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Managing Intraocular Pressure: Innovation in Glaucoma Management

InTech eBooks (2016)

Anne‐Marie Bleau Beatriz Vargas Ana Isabel Jiménez Covadonga Pañeda

Primary open-angle glaucoma is a progressive ocular neuropathy that if left untreated may lead to blindness. The main risk factor for developing glaucoma is increased intraocular pressure. Intraocular pressure is regulated by the balance of aqueous humour synthesis and secretion into the eye and outflow from the eye; therefore, most therapies for glaucoma seek lowering intraocular pressure to avoid disease progression. There are several types of drugs in the market for the treatment of glaucoma, but there are still unmet needs to be overcome; therefore, significant effort has been put in the last few years to develop new medicines with innovative mechanisms of action as well as devices to improve quality of life in glaucoma patients. The present review offers a thorough revision of the latest advances in the glaucoma therapy field, focusing on innovative approaches, new targets and new mechanisms of action.

10.5772/65972

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Citations (3)

Growth hormone-releasing peptide-6 inhibits cerebellar cell death in aged rats

Neuroreport (2003)

Covadonga Pañeda Ana I. Arroba Laura M. Frago Anne Mette Holm John Rømer

Insulin-like growth factor (IGF)-I is essential for cerebellar granule neuron survival and a decline in IGF-I is implicated in various age-dependent processes. Here we show that IGF-I mRNA levels are decreased in the cerebellum of old rats compared with young rats and this was associated with increased cell death and activation of caspases 3 and 9. Growth hormone-releasing peptide (GHRP)-6, a synthetic ligand for the ghrelin receptor, increased IGF-I mRNA levels, decreased cell death and inhibited caspase 3 and 9 activation in the cerebellum of aged rats. These results suggest that increasing IGF-I expression in the cerebellum can decrease cell death in aged rats via inhibition of caspase 3 and 9 activation.

Granule cell

10.1097/00001756-200308260-00018

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Citations (25)

Tivanisiran, a new treatment for Dry Eye Disease, that improved signs and symptoms in clinical trials

Investigative Ophthalmology & Visual Science (2018)

Ana Isabel Jiménez Verónica Ruz Victoria González Covadonga Pañeda Tamara Martı́nez

Signs and symptoms

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Towards the in vitro reconstitution of caveolae. Asymmetric incorporation of glycosylphosphatidylinositol (GPI) and gangliosides into liposomal membranes

FEBS Letters (1999)

Ana V. Villar Alicia Alonso Covadonga Pañeda Isabel Varela‐Nieto Urs Brodbeck

Large unilamellar vesicles consisting of phospholipids with or without cholesterol have been prepared containing GPI and/or gangliosides asymmetrically located in the outer leaflet of the bilayer. Such asymmetric distribution of GPI and gangliosides is found in ‘rafts’ and caveolae. Using these vesicles, GPI can be readily hydrolysed by phospholipases. Both cholesterol and ganglioside are seen to inhibit, in an additive way, the hydrolytic activity of GPI‐specific phospholipase D.

Ganglioside

Lipid raft

10.1016/s0014-5793(99)01010-8

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Citations (16)

Safety and Efficacy Clinical Trials for SYL1001, a Novel Short Interfering RNA for the Treatment of Dry Eye Disease

Investigative Ophthalmology & Visual Science (2016)

J.M. Benítez-del-Castillo Javier Moreno‐Montañés Ignacio Jiménez-Alfaro Francisco J. Muñoz‐Negrete Krista Turman

Purpose: To evaluate the efficacy and safety of SYL1001, a short interfering (si) RNA targeting the transient receptor potential cation channel subfamily V member 1 (TRPV1), for the treatment of dry eye disease (DED). Methods: This study combines a phase I and two phase II clinical trials to test different doses of SYL1001 in a total of 156 healthy subjects and patients with DED. After 10 days of treatment, the primary efficacy endpoints were the effect on (1) the scoring in the Visual Analogue Scale (VAS) and Ocular Surface Disease Index (OSDI) questionnaires, and (2) ocular tolerance evaluated by corneal fluorescein staining and conjunctival hyperemia. Secondary endpoints included the assessment of systemic and local tolerance. Results: Topical administration of SYL1001 1.125% once daily produced a significant decrease in VAS scores compared with placebo from day 4 until the end of treatment (change from baseline at day 10: −1.73 ± 0.32 vs. −0.91 ± 0.34; P = 0.013). For all treatments, OSDI scores were significantly reduced compared to their respective baseline values (P < 0.01), although no significant changes were detected between groups. Conjunctival hyperemia (quantified as normal or abnormal) significantly improved after instillation of SYL1001 1.125% compared with placebo (50% vs. 20%; P < 0.05). Excellent tolerability was reported, with no differences in the rates of occurrence of adverse events between groups. Conclusion: These trials achieved their primary endpoints of identifying the most effective dose of SYL1001 (1.125%). SYL1001 showed a large safety margin and may provide novel therapeutic opportunity for the relief of dry eye. (ClinicalTrials.gov numbers, NCT01438281, NCT01776658, and NCT02455999.)

Tolerability

Clinical endpoint

Therapeutic effect

10.1167/iovs.16-20303

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Citations (84)

The Corticotropin-Releasing Factor-Hypocretin Connection: Implications in Stress Response and Addiction

Drug News & Perspectives (2005)

Covadonga Pañeda Raphaëlle Winsky‐Sommerer Benjamin Boutrel Luı́s de Lecea

The hypothalamic neuropeptides hypocretins (orexins) play a crucial role in the stability of arousal and alertness. Recent data have raised the hypothesis that hypocretin neurons are also part of the circuitries that mediate the hypothalamic stress response. In particular, we have recently demonstrated that corticotrophin-releasing factor (CRF)-immunoreactive terminals make direct synaptic contacts with hypocretin-expressing neurons and that numerous hypocretinergic neurons express the CRF-R1/2 receptors. Furthermore, CRF excites hypocretinergic cells ex vivo through CRF-R1 receptors. Activation of hypocretinergic neurons in response to acute stress is severely impaired in CRF-R1 knockout mice. Moreover, the stress response is impaired in hypocretin-deficient mice. We propose that upon stressor stimuli, CRF stimulates the release of hypocretins, and this circuit contributes to activation and maintenance of arousal associated with the stress response and addiction.

Alertness

Stressor

Knockout mouse

10.1358/dnp.2005.18.4.908659

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Citations (32)

Clinical and preclinical study correlation for SYL1001, a new treatment for dry eye disease

Investigative Ophthalmology & Visual Science (2017)

Victoria González Verónica Ruz Covadonga Pañeda Anne‐Marie Bleau Beatriz Vargas

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Purification and Characterization of Insulin-Mimetic Inositol Phosphoglycan-Like Molecules From Grass Pea (Lathyrus sativus) Seeds

Molecular Medicine (2001)

Covadonga Pañeda Ana V. Villar Alicia Alonso Félix M. Goñi F. Varela

Signal transduction through the hydrolysis of glycosyl-phosphatidylinositol (GPI) leading to the release of the water-soluble inositol phosphoglycan (IPG) molecules has been demonstrated to be important for mediating some of the actions of insulin and insulin-like growth factor-I (IGF-I). In the present study, GPI from grass pea (Lathyrus sativus) seeds has been purified and partially characterized on the basis of its chromatographic properties and its compositional analysis. The results indicate that it shows similarities to GPI previously isolated from other sources such as rat liver. IPG was generated from L. sativus seed GPI by hydrolysis with a GPI-specific phospholipase D (GPI-PLD). This IPG inhibited protein kinase A (PKA) in an in vitro assay, caused cell proliferation in ex-planted cochleovestibular ganglia (CVG), and decreased 8-Br-cAMP-induced phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression in cultured hepatoma cells. Our data indicate that L. sativus seed IPG possess insulin-mimetic activities. This may explain why L. sativus seeds have been used in some traditional medicines to ameliorate diabetic symptoms.

Lathyrus

10.1007/bf03401850

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Citations (12)

Short-interference RNAs: becoming medicines.

PubMed (2015)

Tamara Martı́nez Ana I. Jiménez Covadonga Pañeda

RNA interference is a cellular mechanism by which small molecules of double stranded RNA modulate gene expression acting on the concentration and/or availability of a given messenger RNA. Almost 10 years after Fire and Mello received the Nobel Prize for the discovery of this mechanism in flat worms, RNA interference is on the edge of becoming a new class of therapeutics. With various phase III studies underway, the following years will determine whether RNAi-therapeutics can rise up to the challenge and become mainstream medicines. The present review gives a thorough overview of the current status of this technology focusing on the path to the clinic of this new class of compounds.

RNA Silencing

10.17179/excli2015-297

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Citations (20)

Silencing human genetic diseases with oligonucleotide-based therapies

Human Genetics (2013)

Tamara Martı́nez Natalia Wright Marta López‐Fraga Ana I. Jiménez Covadonga Pañeda

Human genetics

Identification

10.1007/s00439-013-1288-1

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Citations (49)