Another factor of success is that both CEM and SSIF are focused on including every year improvements and new educational tools. Last, but not least, the sincere enthusiasm that Xavier Montalban and all his collaborators show working on this project. Among the "new entries", in this 2009 Summer Edition, there was the outstanding key note lecture delivered by Reinhard Hohlfeld, combining an extremely updated basic knowledge of immunopathology of MS with stimulating focuses on present and future therapeutic targets. This was followed with a general overview as well as recent findings of the epidemiology, genetics and pathology of multiple sclerosis. Oscar Fernandez in the former concluded his presentation by mentioning that MS is increasing in Southern Europe and the analysis of the factors influencing this change would be of great interest to find the causes of the disease. Manuel Comabella mentioned that there are genes located outside the HLA region that, unfortunately only with weaker effects, are solid candidates for MS genetic risk, something that could open new scenarios in MS genetic research. Christine Wenger's excellent talk which followed, mentioned that there is evidence for significant white and grey matter damage in MS. Limitation of this pathology is important and may require anti-inflammatory as well as neuroprotective treatment approaches. After the overview of MS clinical forms and variants from Alejandro Horga, the session ended with Angleo Ghezzi's talk on juvenile MS.
In the afternoon participants were split into two groups: one went to the rehabilitation center and the other visited the clinical facilities and research labs of Val d'Hebron Hospital complex. This was followed by a Case Study Session which was organized in a 15 minute plenary session for the presentation of the three case studies by the Chairman. The presentation of each case included a couple of slides on the patient's history and one slide with a few points on the related management to be discussed in each working group. Participants were then split in three working groups to discuss different solutions to answer to the issues on each case. This was followed by another 15 minute plenary session with Case Presenters showing the solutions proposed by each working group for a general discussion. This pattern was repeated also for day two.
Many diagnostic criteria have been proposed in last decades and technology offers continuously improved imaging and laboratory tests, but MS diagnosis is clinical, as showed in an exhaustive and elegant way Mar Tinoré in her lecture. Alex Rovira stated that magnetic resonance imaging is now integrated in the overall diagnostic scheme of the disease because of its unique sensitivity to demonstrate the spatial and temporal dissemination of demyelinating plaques in the brain and spinal cord. Maria Pia Sormani then explained the methodological issues from current MS trials and Jaume Sastre-Garriga, who in his talk on symptomatic treatment and neurorehabilitation in MS, concluded that further research is needed to improve clinical trial methodology and our ways of evaluating the impact of neurorehabilitation by means of goal achievement frameworks and through the use of clinically appropriate and scientifically sound outcome measure tools. Two talks on two effects on MS and relative rehabilitation followed: gait disorders and dysphagia.
The final two lectures of the session on cognition disorders were delivered by Maria Pia Amato and Alan Thompson. The former underlined that the search for effective therapeutic strategies is an urgent priority for future research whereas the latter mentioned that cognitive rehabilitation is still in its infancy and more methodologically rigorous research is needed to determine the efficacy of specific therapeutic interventions.
The final day was opened by Carmen Tur with an overview of currently registered drugs for MS who mentioned that regarding future directions, stem cell therapy is to be considered to find the cure for MS. This was followed by two lectures on the definition of treatment failure and by a presentation on the fundamental nurses' role in the management of MS patients by Rosalía Horno and Gemma Rodríguez. The highest educational moment of the event was probably the role-play with the patient which came next. María Jesús Arévalo and Jaume Sastre-Garriga provided participants with "take at home" tools to foster adherence to treatment, a crucial factor for a successful long-term management.
The afternoon started with the second key note speech from Giancarlo Comi. The President of SSIF Scientific Committee stated that there is a need to start escalating treaments in the early phases of the disease because of the best efficacy/safety profile of immunomodulatory agents. Furthermore intensive immunosuppressions as well as combination therapies - under evaluation with 28 ongoing trials - are further options. An outlook on future therapies from Roland Martin and the wrap up Xavier Montalban concluded the three-day preceptorship.
The MS Preceptorship success is also due to the limited number of participants that favour the interaction and to fulfil all the registration requests SSIF will organize a Fall Edition of the course from November 3-5.
Tommaso Sacco & Simon Basten
Click here for the Presentations!
David Bates, Professor of Clinical Neurology, University of Newcastle upon Tyne and Consultant in Neurology, Newcastle upon Tyne Hospitals NHS Foundation Trust. My commitments to people with multiple sclerosis are twofold: firstly providing a service with the help of colleagues, registrars, MS nurses, psychologists and physiotherapists for people with multiple sclerosis and compiling important demographic data from the cohort. Part of this clinical service involves trials of new agents in phase II and phase III trial and the continuing monitoring of people taking disease modifying therapy as part of the UK Risk Sharing Scheme. Secondly in the laboratory we have post-doctorial fellows working on the nature of mitochondrial disturbances arising in denuded axons with the hope that we shall be able to identify and amend those factors which lead to secondary degeneration of axons and neurones later in multiple sclerosis.
What are the most importance evidences collected recently on the pathophysiology of MS?
There are several recent innovations in understanding the pathophysiology of multiple sclerosis. The most important is unquestionably the identification of a causative humoral agent, the antibody to aquaporin 4, in a majority of people with neuromyelitis optica, suggesting that it differs from classical multiple sclerosis. In addition, the finding of germinal centres in the meninges of people with multiple sclerosis helps to explain the persistence of oligoclonal bands in the cerebro-spinal fluid and raises the possibility of more important B-cell function in the disease. The debate between those pathologists who perceive different pathological appearances of lesions as being specific to individuals and those who believe they change through time is instructive and the disagreements and arguments ensuing are themselves productive of new ideas and concepts.
Do you think this evidence of pathophysiologicy will be useful in defining new pathocological targets?
The possibility of involving B-cell therapies is already important and understanding of the nature of the damage that results in secondary degeneration will hopefully produce pharmacological agents or biotechnical products which can improve neuro-protection, encourage repair and possibly provide remyelination.
Will the evolution of diagnostic criteria help neurologists in defining better MS diagnoses?
The evolution of diagnostic criteria is a mixed blessing, in one respect it helps to define more precisely the nature of a condition, but it is liable to mis-use. The possible exclusion of rare forms and conditions which might give important information as to the underlying pathophysiology should be of concern. It is more likely that understanding pathophysiology, rather than redefining diagnostic criteria, will be productive.
What are the main challenges?
During the next few years several new disease modifying therapies will enter the market. All should be as effective as or more effective than the currently available agents and all will be more convenient, being either oral or requiring infrequent infusions. The dilemma will be due to questions safety. As agents of increased potency are used there will be an increased risk of intercurrent infection, opportunistic infection and the potential for neoplasia. It will be many years before the underlying safety of these agents is established. The new drugs will also raise the possibility of changing use of therapy, either with combinations in treatment or, more probably, with the concept of induction of a relative disease free state and then its maintenance by other agents. The final interesting point in the next few years is that several of the agents which are being developed are already available in different forms at much lower prices than those currently charged for disease modifying therapy. The way in which this is handled by the licensing and reimbursing authorities will be of interest.
Thank you very much.
The first session of the event was opened by a stimulating lecture form Paul Devroey on current low rate of fertility in Europe followed by a couple of speeches focused on main genetic markers influencing the reproductive function (genotypes and polymorphisms associated with male infertility and abnormal ovarian response) and on potential predictors for IVF success (age, stress, habits, etc). Jorge Chavarro, from Harvard Medical School drove the audience’s attention to nutrition and lifestyle as important factors associated to infertility. The session was concluded by Juan Antonio Garcia-Velasco who presented a strategic list of practical recommendations on how to increase patient’s compliance and to reduce treatment drop out rates.
In the second session many crucial aspects of ovarian stimulation were addressed to the audience: individualization of stimulation regimens, prognostication of ovarian reserve, as well as treatment strategies for poor responders were carefully analyzed in order to establish well defined goals for ovarian response stimulation and to identify personalized treatments. Lastly, some important data and practical suggestions on how to reduce ovarian hyperstimulation in high risk ART patients were provided by Antonio Pellicer.
The third part of the congress went through the procedures able to improve cycle outcomes. Hilde Van De Velde started the session by examining, even from a legal point of view, the HLA (Human Leukocyte Antigen) typing on human pre-implantation embryos. Impact on human IVF outcomes of oocyte cryopreservation procedures, from pre- to post-storage methods, as well as its data comparison with embryo freezing routine techniques were also presented.
The final lectures of this session were focused on fertility preservation (oocytes, sperm, or ovarian tissue cryopreservation) in patients undergoing cancer treatments and on future perspectives in ART techniques, starting from the upcoming contribution to ART by genomics and transcriptomics to the creation of mature gametes from stem cell lines.
The brilliant final panel discussions with a strong participation from the involvement of attendees concluded the course.
Luca Megas
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The introductory lecture from Stephen Shalet reviewed the issues related with the discontinuation of growth hormone (GH) in subjects that have reached the final height. Hugo Fideleff and Mark Molitch dealt with the diagnostic criteria of GHD in childhood and in adulthood, respectively. The conclusion of these excellent reviews was that laboratory assessment must be supported by careful clinical evaluation.
Fernando Cassorla in his talk addressed both therapeutic protocols for GHD treatment in childhood as well as criteria to evaluate response. After an exhaustive overview of genetics of GHD delivered by Raul Calzada, Stephen Shalet dealt with another debated topic: “Partial GHD”. He concluded his presentation by stating that partial GHD does exist, in particular as a consequence of putative insult to hypothalamic – pituitary axis, and that it’s hormonal phenotype is in some way intermediate between those of normal and GHD patients. He also suggested that partial GHD is difficult to diagnose in the majority of patients in whom IGF-1 level is normal.
A panel discussion on major issues in GHD management related to regulatory and reimbursement rules in Latin America gave the opportunity, to speakers and participants, to share issues as well as discuss solutions aimed at improving the management of GHD patients.
The last sessions of the Symposium covered three more interesting aspects of GHD treatment. Roberto Lanes, the Scientific Organizer of the meeting, addressed the alteration of endothelial function that in GHD subjects increases the risk of metabolic and cardiovascular diseases. Cesar Luis Boguszewski gave an exhaustive overview of complex relationships among GH and IGF-I levels and bone and muscle physiology and Mark Molitch closed the meeting with an outstanding lecture on GHD management in adulthood.
Tommaso Sacco
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After completing my study at the University of Zagreb, Croatia, I specialized in Clinical Chemistry at the University Hospital in Zürich, Switzerland. Subsequently I finished my Ph.D. in Biochemistry at the University of Zürich with the thesis entitled “Characterization of two new inborn errors of metabolism: Gly-Pro-Hyp-Gly-aminopeptidase and GTP cyclohydrolase I deficiency” and started as a head of Clinical Chemistry and Mass Spectrometry services at the same institution. At that time I also started my research in tetrahydrobiopterin (BH4) metabolism. In 1990 I was appointed as a head of the Laboratory for Selective Screening of Metabolic Disorders at the University Children’s Hospital of Zürich and in 1995 a habilitation in Clinical Biochemistry entitled “The Hyperphenylalaninemias: A differential diagnosis and international database of BH4 deficiencies” was approved by the Faculty of Medicine at the University of Zürich. At the same time I was appointed as a lecturer in Clinical Biochemistry and Cell and Tissue Biology at the University of Zürich. More than 200 research publications and standard books like “Physician’s Guide to the Laboratory Diagnosis of Metabolic Disease”, “Physician’s Guider to the Treatment and Follow-up of Metabolic Diseases", and “Laboratory Guider to the Methods in Biochemical Genetics” published in three English and one Chinese editions document the research done at the Children’s Hospital in Zürich. I am also the Chairman of the upcoming Serono Symposia International Foundation Advances and Challenges in PKU which will take place in Munich on January 21-22, 2010.
What are your main fields of interest?
My research is focusing on the characterization of BH4 deficiency variants on both the protein and the DNA levels. In collaboration with colleagues at the Children’s Hospital in Zürich and with many clinics worldwide we introduced new diagnostic tests and established new treatment protocols for BH4 and biogenic amine neurotransmitter deficiencies. Besides BH4, my research interests include Phenylketonuria (PKU), nitric oxide metabolism and cardiovascular diseases, and folate metabolism. In 1992 an International Database of Tetrahydrobiopterin Deficiencies (BIODEF) was initiated and since 1997 I am a curator of the three online BIOPKU, BIODEF and BIOMDB databases, all accessible from the www.biopku.org website. In the last 25 years my research was highlighted by the discovery of pterin-4a-carbinolamine dehydratase deficiency, sepiapterin reductase deficiency, a form of BH4 deficiency presenting without hyperphenylalaninemia, and by molecular characterization of the mild form of dihydropteridine reductase deficiency.
Of particular interests are patients with BH4-responsive PKU. These are patients with specific mutation in the PAH gene, coding for the defective enzyme phenylalanine hydroxylase, which can potentially benefit from the substitution with a synthetic form of BH4 (sapropterin, Kuvan®). We are now investigating molecular mechanisms underlying BH4 responsiveness, developing genotype-predicted characterization of patients’ phenotype, and optimizing diagnostic and treatment approaches.
What should every doctor know about phenylketonuria management?
It is extremely important to know for every doctor that PKU is a treatable disease and that different treatment options exist today. The implementation of newborn screening to detect PKU has facilitated the early use of dietary treatment, resulting in near normalization of outcomes of individuals with PKU. Today we know that maintaining the restricted diet is beneficial if not essential to prevent brain damage, but there are still disagreements as to how long this diet should be continued. A number of nutritional products with improved quality are available in most countries, but many adolescents and young adults generally do not comply with the recommendations for monitoring and control of phenylalanine concentrations, and two thirds of pregnant women in the United States did not follow the diet before becoming pregnant. Thus there is an urgent need for alternative approaches to treat PKU patients and sapropterin treatment, combined with diet or alone, is the newermore recent one and Kuvan® is the first commercially available pharmacological option.
How will the introduction of drugs in the management of PKU modify the approach to the disease?
Several controlled clinical trials have evaluated the efficacy of a pharmaceutical formulation of sapropterin, in patients with PKU. Overall, the results of these trials, including previous investigations with BH4, indicated that about 20–50% of patients with PKU (depending on the phenotype) achieved a reduction in blood Phe of ≥30%. Consequently, sapropterin can be used for the treatment of hyperphenylalaninemia in patients with PKU who have been shown to be responsive to such treatment. Thus, all patients with PKU should undergo a sapropterin oral-response test before treatment initiation and as next decision needs to be made wheather treatment is necessary and what kind of treatment need to be used.
How will new approaches to disease management improve the life of PKU patients?
Sapropterin can significantly improve the management of patients with milder or moderate forms of PKU who respond to this treatment. The decision to combine sapropterin with a Phe-low diet, or to introduce a monotherapy with sapropterin, is based on the individual Phe tolerance and on the targeted therapeutic range for blood Phe levels. Regardless of the mode of administration, sapropterin can improve the quality of life of BH4-responsive PKU patients.
Thank you very much.
Disease patterns in the three disorders - Alzheimer, Parkinson's and Multiple Sclerosis - are very different one from another despite the categorization into a general definition. In some case, the differences are so marked that it can support the hypothesis that each neurodegenerative disorder includes a cluster of disease. The aim of the symposium was to summarize evidences this approach is based on and stimulate the discussion.
Lars Betram introduced Alzeihmer's disease (AD) with a detailed background on the genetic epidemiology of AD, highlighting the currently most compelling genetic risk factors and their possible pathogenetic implications. He continued by putting particular focus on loci and on the emerging field of genome-wide association studies (GWAS) and their potential in resolving the complex genetic architecture underlying most forms of AD.
Thomas Gasser spoke about Parkinson's disease (PD) and the fact that over the last few years several genes for monogenic forms of PD have been mapped and/or cloned. Studies have determined that there is an increasingly complex network of genes emerging all of which are contributing to disease risk and progression.
Jan Hillert concluded the symposium by speaking of multiple sclerosis (MS). He mentioned that there is a striking number of MS genes with an importance for immune functions and the similarity in risk genes between different autoimmune diseases strongly supports the concept that MS has indeed an autoimmune origin, thus supporting the ongoing efforts to improve immunomodulatory treatments in MS.
Tommaso Sacco & Simon Basten
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On the route of optimization of infertility treatment, many tools have become available to profile individual response to treatment according to couples' characteristics and therefore tailor IVF procedures. The aims of this conference are to review the knowledge the patient tailored approach is based on and to provide indications on how to implement this approach in clinical practice.
The objective of this course is to provide participants with the most updated knowledge on IVF procedures and with skills useful in IVF practice using an interactive format with a strong emphasis on discussions between the faculty and the participants.
There is a special registration dedicated to oncologists, paediatricians, radiotherapists to attend December 10 (only 1st day meeting). For more information click here for oncologists and here for paediatricians.
This is an educational programme created to encourage the dissemination of scientific knowledge in the field of MS. It will stress the benefits of new diagnostic tools for defining the natural history of MS and disease activity monitoring. Current diagnostic criteria for MS will also be reviewed in the light of new medical evidence. A review of recent clinical trials and treatment optimisation guidelines will also be presented.
This is an educational program created to encourage the dissemination of scientific knowledge among nurses from all over the world in the field of MS.
The objective of this workshop is to provide its participants with up-to-date knowledge on multiple sclerosis (MS) and to offer the possibility to share clinical practice issues and solutions with top level experts and highly qualified participants.
The outcomes of researches on pathophysiology of MS and availability of new drugs with innovative mechanisms of action are changing the knowledge on the disease and will offer new management options. The aim of the Symposium is to provide participants with updates on patient selection and treatment planning in order to tailor the management according to patients and diseases characteristics.
Present and future efforts on phenylketonuria (PKU) treatment will be discussed in this event particularly with regard to new pharmacological approaches, such as enzyme substitution and cofactor administration. The importance of patient management will also be highlighted, both in PKU as well as in tetrahydrobiopterin deficient patients. Furthermore, the workshop sessions will offer the possibility to discuss knowledge and experiences on six major aspects of PKU management.