Serono Research Grants, 2007
The Merck Serono Research Grants 2006 were presided over by Mr. Bernat Soria Escoms, Minister of Health and Consumer Affairs and awarded to 5 projects from the following Research Fields: Clinical Research in Endocrinology, Clinical Research in Infertility, Clinical Research in Multiple Sclerosis, Clinical Research in Psoriasis, Clinical Research in Oncology and Research in Rare Diseases.
The winners of this edition’s different categories are the following:
Field of Infertility Clinical Research
Research Project:
Vitrification of oocytes with very low concentrations of cryoprotectors based on the technology of quartz microcapillaries
Main researcher:
Dr. Ramón Risco Delgado
Project Summary:
Purpose: There are several cell types that today cannot be cryopreserved satisfactorily. One of the most important examples are oocytes. Although “slow freezing” is the method most commonly used, vitrification is now an extremely interesting option. However, the high concentration of cryoprotector required for an adequate vitrification is often toxic for this cell type. The purpose of this project is to show the efficacy of a new vitrification technique, developed by Risco et al., that will probably mean the end of the problems around cryopreservation of these gametes. By the use of quartz capillaries employed in microfluids and X ray diffraction, high cooling rates and concentrations of cryoprotector typical of “slow freezing” (not toxic), it has been shown that vitrification can be achieved. The cooling rate obtained (250,000 ºC/min) is far faster than that achieved with other methods (20,000 ºC/min), keeping the characteristics of the container of “vial” type, that offers so many advantages over other types of containers (electronic microscopy copper grids, Crioloops, etc.). The aim of this project is to set up the technique for an immediate clinical application in the field of assisted reproduction. This achievement would mean a major advance in the preservation of fertility in women who decide to delay maternity or those receiving chemotherapy, radiation therapy or ablation therapy. In addition, this would allow for setting up oocyte banks, overcoming the ethic and legal problems around preservation of embryos.
Methods: murine oocytes (F1) in metaphase II (previously denuded) will be loaded in several stages with non-toxic concentrations of cryoprotectors (1.5 M PrOH and 0.3 M sucrose (Fabbri et al., 2000 2001). Then, they will be transferred to quartz microcapillaries and placed in cryogenic mixes specially manipulated (Patent no. P200702565, University of Seville). For storage, oocytes will be transferred to liquid nitrogen where they can be kept until they are used. When the oocytes are required, they will be transferred from the quartz microcapillaries to solutions with decreasing concentrations of PrOH to reach normal culture conditions. After several viability tests on them, they will be fertilized and transferred. After proving the superiority of this technique over the current options, the improvements provided (including reduction to non-toxic levels of the concentration of cryoprotectors) over the protocols of vitrification of human oocytes will be introduced. An automatism specifically designed for it will commit with the repetitiveness of the process.
Jury:
Field of Multiple Sclerosis Clinical Research
Research Project:
Expression natural killer cell receptors in T lymphocytes in patients with multiple sclerosis
Main researcher:
Dr. José Enrique Martínez Rodríguez
Project Summary:
Introduction: Recent studies in chronic inflammatory diseases show that the expression of natural killer (NK) cell receptors in T lymphocytes can contribute to the development of autoimmune phenomena. However, the implication of NK receptor expression in multiple sclerosis (MS) and the expression pattern of these receptors in CD4+ T lymphocytes specific for Epstein-Barr virus (EBV), one of the main agents involved in the aetiology of the disease, is unknown.
Hypothesis: The expression of NK receptors in T lymphocytes can modulate the response of these cells to pathogens and autoantigens, and can be related to the inflammatory activity of MS. With regard to the etiological hypothesis of the disease, the expression pattern of NK receptors in CD4+ T lymphocytes specific for human EBV and cytomegalovirus (CMV) could differ between healthy subjects and patients with MS.
Purpose: To evaluate in patients with MS the expression of NK cell receptors in CD8+ and CD4+ T lymphocytes, and in CD4+ T lymphocytes specific for EBV and for cytomegalovirus (CMV), relating the expression of these receptors with clinical parameters of inflammatory activity and progression.
Methods: The expression of activating and inhibitory NK receptors (NKG2D, ILT2, KIR, CD94/NKG2A and CD94/NKG2C) will be tested in mononuclear cells obtained from peripheral blood at baseline in CD8+ and CD4+ T lymphocytes, and in CD4+ T lymphocytes specific for CMV and EBV expanded in culture in vitro with a stock of human CMV and a commercial lysate of EBV, through triple-colour labelling by immunofluorescence with monoclonal antibodies specific for NK receptors. The percentage of expression of NK receptors will be compared between control subjects and patients with MS, and will be correlated to various clinical variables.
Expected results: The pattern of expression of NK receptors in T lymphocytes would be related to the activity of the disease and would be a prognostic marker of inflammation / disability in multiple sclerosis.
Jury:
Dr. D. Jordi Matías-Guiu, Dr. D. Rafael Arroyo González, Dr. D. José Carlos Álvarez Cermeño, Dr. D. Jesús Merino, Dra. Dña. Blanca Pinilla, Dr. D. Xavier Montalbán, Dr. D. Txomin Arbizu.
Field of Endocrinology Clinical Research
Research Project:
Identification by proteomics of new adipokines and myokines involved in human obesity
Main researcher:
Dra. María Pardo Pérez
Project Summary:
In recent years, the prevalence of obesity in the world is undergoing an exponential increase, reaching a pandemic extent. Spain is not free from this problem and it is already the tenth country more obese of the world, according to comparative OCDE data. The overall objective of this project is to test new systems of signals of the adipose (adipokines) and muscular system (myokines) responsible for deregulation of energetic homeostasis in obesity. For this, it is proposed to apply proteomics as a new emerging technology, which is very useful in the identification of new target proteins in various diseases. The identification of new signal proteins secreted by the adipose and muscular tissues will allow for improving the knowledge of the mechanisms regulating energetic homeostasis and body weight as an essential part for an adequate treatment of obesity. The objectives are as follows:
1) Set up of in vitro models for the study on the secretion or secretomes of fat and muscle tissue from explants from thin individuals and those with various degrees of obesity.
2) Application of proteomic techniques to the differential study of secretomes from adipose and muscle tissue from thin individuals and those with different degrees of obesity.
3) Study on the differential proteome of adipose and muscle tissue in the same patients.
4) Evaluation and validation of proteins previously obtained as new signal systems of the adipose and muscle tissue in obesity. The presence of new signals identified in serum from obese and thin individuals to demonstrate specificity and clinical value.
Jury:
Field of Psoriasis Clinical Research
Research Project:
Changes in the cardiovascular risk profile in patients with psoriasis treated with biological products
Main researcher:
Dra. Lucía Martínez Casimiro
Project Summary:
In recent years, there have been multiple studies on the so-called metabolic syndrome, an entity comprising various cardiovascular risk factors, such as hypertension or insulin resistance that appears to cause a risk increase far higher than the sum of the risk factors making it up.
The relation it is intended to establish between psoriasis and metabolic syndrome and an increase in the cardiovascular risk are even more innovative. It has been intended to relate genetically the metabolic syndrome and psoriasis, but it only appears to be true that there is an increased prevalence of metabolic syndrome vs the general population or other dermatological populations according to the studies published. Currently it has not been well defined if the increase is due to the disease per se, to the chronic inflammatory disease, or the role played by the different treatments, since these causes changes in up to 80% of the patients, such as hypertransaminasemia, hypertension, hyperlipidemia, changes in renal function and photosensitivity, or even the role of the lifestyle of these patients.
Patients with psoriasis starting treatment with a biological agent are currently patients that, according to the data sheet, show moderate-serious psoriasis and have used at least 2 classic systemic drugs. If these drugs cause permanent disorders after their use, our group of patients would be similar for them. Recent studies discuss the possibility that these new biological agents improve the cardiovascular profile risk in these patients. The aim of this study is to analyse the cardiovascular risk profile, including a study on metabolic syndrome in patients with psoriasis that will first start treatment with a biological agent and see how this profile changes over one year from the treatment and comparing patients to themselves and to a control group. The aim is to show if the use of biological agents involves any benefit for the cardiovascular profile and whether it enhances therapeutic actions on the matter, given the significant impact for this group in terms of quality of life and life expectancy. The study will be performed analysing the data obtained in the daily clinical practice, from the clinical history, anthropometric data and several laboratory tests, in addition to an electrocardiogram (ECG), impedance measurement, and oral glucose overload curve. The data will be analysed using different statistical analysis systems, mainly SPSS 15.0. The project introduced is a pilot project for which we think thirty patients in each group will be enough to identify clinically significant differences.
Jury:
Field of Oncology Clinical Research
Research Project:
Prognostic value of circulating tumour cells in patients with metastatic breast cancer
Main researcher:
Dr. Miguel Martín Jiménez
Project Summary:
The identification of circulating tumour cells has significant prognostic and therapeutic implications. The presence of circulating tumour cells could be of value for the following reasons: in the initial evidence of the metastatic condition, such as a marked risk of possibility for metastatisation and, therefore, indicator of poor prognosis and marker for monitoring treatment response.
The aim of this project is the identification, quantification and study of the prognostic role of tumour cells in peripheral blood in patients with metastatic breast cancer before starting chemotherapy.
It is a prospective cohort study. For this, 60 patients with metastatic breast carcinoma will be selected. A baseline sample is obtained prior to APRA chemotherapy to establish the follow-up for the purpose of relating circulating tumour cells with the prognosis and response to adjuvant therapy.
Jury:
Field of Rare Diseases Research
Research Project:
Validation of a Quantitative Clinical Neuromuscular Evaluation System for application in clinical trials in patients with amyotrophic lateral sclerosis
Main researcher:
Dr. Jesús S. Mora Pardina
Project Summary:
The aim of the project is the definition, validation and subsequent clinical application of a specific Quantitative Neuromuscular Assessment Protocol, called MAQUINA (MAdrid QUantative Neuromuscular Assessment) in patients with Amyotrophic Lateral Sclerosis (ALS). This protocol will include measurements of isometric muscle strength in specific muscle groups by an electronic strength transducer, bulbar function tests, respiratory functions tests, and timed tests on specific motor functions performed in the upper and lower extremities.
It is intended that the technical measurement error made with this protocol is lower than with the efficacy variables commonly used in clinical trials (such as the manual muscle balance or ALS Functional Rating Scale), and thus reduce the sample size and the follow-up time required to detect a positive effect of the treatment.
The relatively low number of patients with ALS and the cost of requiring a high number of patients with long follow-up times makes it difficult to perform clinical trials in ALS. The MAQUINA protocol can enhance fast, less costly trials, even promoted by the investigators, with drugs already marketed and with a mechanism of action that can be considered of possible benefit in this terminal disease.
Jury:
