Col6.it: with a view to a more extensive, eye-catching and multi-disciplinary profile
Summary of the fourth meeting of the col6.it Group, held on 12th November in the Centro Sociale Ricreativo e Culturale A. Montanari in Via di Saliceto, 3/21, 40128 Bologna
by Ilaria Gregorio & Martina Chrisam
The fourth meeting of patients, doctors and researchers in the col6.it Group was held on 12th November in the Centro Sociale Ricreativo e Culturale A. Montanari in Bologna and, as usual, it turned out to be a unique opportunity for discussion with regard to the variety of real-life situations in the context of
Collagen VI related myopathies. On this occasion, the scientific debate went beyond the usual confines of the topics most closely linked to the muscular aspects of these pathologies, and saw the participation of experts from various fields of study who gave talks not only on certain biomedical but also on the economic aspects of scientific research. In addition, we also had the opportunity to listen to representatives from UILDM and Telethon, who will offer invaluable assistance to enhance the profile of the Group. Now let’s take a look at the most significant events of the day.
Cecilia Sorpilli, the backbone of the Group and organiser of the event, begins by extending a warm welcome to the participants and gives a brief summary of the situation of the Group, which is constantly growing. Her introduction is followed by a speech given by Dr. Luciano Merlini, who provides us with a detailed explanation of the advantages and disadvantages involved in the Cyclosporine A therapy administered to patients affected by Bethlem Myopathy and Ullrich Congenital Muscular Dystrophy. While being extremely effective in remedying the defects of the energy-producing mitochondria in the muscle cells, this drug however has the by no means negligible disadvantage of considerably weakening the patient’s immune system.
The next person to speak is Prof. Paolo Bonaldo, a researcher who detains the merit of having produced a type of mouse with a deficit of Collagen VI. As illustrated in previous meetings, these animals represent an excellent model for the study of human pathologies deriving from a Collagen 6 deficit, because they mimic the muscular weakness afflicting both Bethlem and Ullrich patients. With the invaluable aid of this animal model, Prof. Bonaldo’s laboratory co-workers are engaged on various levels in the study of the effects of Collagen VI deficit not only on the skeletal muscle but also on other organs and tissues.
The young Ph.D. candidate, Ilaria Gregorio, illustrates part of the study undertaken by Matilde Cescon, a senior post-doctoral researcher in Prof. Bonaldo’s laboratory. This study sheds light on the importance of Collagen VI in maintaining the structure and function of the so-called “peripheral” nerves which, on reaching the skeletal muscle, co-ordinate its activity by conveying the nervous impulses from the brain.
Matilde has discovered that in Collagen VI deficient mice these nerves are not endowed with the appropriate electrical isolation; this is due to flaws in the structure of the biological isolator, known as the myelin sheath, for which reason the transmission of nervous impulses is slowed down, thus producing a defect in the motor function, as well as in the sensitivity towards external stimuli such as cold and pain. Matilde is also involved in the study of the role of Collagen VI in the structures acting as interfaces between the peripheral nerves and the muscular fibres, namely the neuro-muscular junctions. In this case, too, Collagen VI deficient mice present structurally altered junctions, abnormally fragmented, which lack the power to ensure the correct transmission of nervous impulses to the muscle fibres, thus giving rise to problems in muscle contraction. Not only have these findings clarified the previously unknown role of Collagen VI in tissues that are different from muscular tissue, that is to say the peripheral nerve, but they provide useful insight as regards the effects of new types of therapy for Collagen VI related pathologies.
Ilaria also mentions another branch of research currently pursued in Prof. Bonaldo’s laboratory, namely the experiments conducted on the tropical fish Danio rerio (commonly known as the zebrafish), targeted towards the study of the role of Collagen VI during embryonic development. This study was initially undertaken by a young post-doctoral member of the laboratory, Valeria Trapani, who recently entrusted the task to the new Ph.D. candidate Valentina Tonelotto. The zebrafish offers the advantage of being totally transparent during the initial stages of embryonic development and, moreover, fertilization takes place in the external environment, for which reason these studies require no invasive procedures on the animals themselves. Valeria has been working on the task of producing, with the use of avant-garde technology, zebrafish devoid of Collagen VI and is now collaborating from her new location (Brisbane in Australia) with Valentina in Italy in order to gain a deeper understanding of what happens to these fish. Preliminary data would seem to indicate that even in fish the development of the skeletal muscle is severely compromised in the absence of Collagen VI.
Subsequently Dr. Andrea Vianello, a pneumologist in the Respiratory Physiopathology Unit in Padua
Hospital, gives an overview of the respiratory complications encountered by patients affected by muscular dystrophies, in particular Ullrich Congenital Muscular Dystrophy. Dr. Vianello illustrates the mechanisms leading to the onset of respiratory insufficiency which, in the case of dystrophy, is not caused by abnormalities in the lungs, but in the respiratory pump, that is to say, the structure formed by muscles, including the diaphragm, which, when in motion, allows air to enter the lungs. Then Dr. Vianello outlines the progress attained in recent years thanks to devices for non-invasive mechanical ventilation, which have enabled doctors to make enormous improvements in the life expectancy of patients affected by dystrophy with respiratory insufficiency, even in the most severe cases, such as in muscular spinal atrophy.
The next speaker to take the chair is Prof. Renzo Orsi, an economist from the University of Bologna, who illustrates the mechanisms whereby certain drugs prove to be particularly expensive. His talk is centred on the drug Sofosbuvir (marketed under the name of Sovaldi), a new drug used to treat hepatitis C. This
is a drug that is particularly effective in eradicating the hepatitis C virus, but the problem is that in the United States the cost of a four-week course of treatment amounts to 85 thousand dollars per patient, whereas in Italy the cost is approximately 30 thousand euros. It seems clear that, given the elevated number of patients affected by hepatitis C, our National Health Service – which is still among the best in the world – is not in a position to provide all patients with this treatment, with the result that most patients would have to pay out of their own pockets. The Sofosbuvir issue has given rise to heated discussions in and outside Italy, but why is it that it costs so much? Prof. Orsi explains that the high cost of drugs depends on the amount of money that has been invested during their development phase, which generally spans over 10 to 12 years. In the case of Sofosbuvir, the small pharmaceutical company that developed it, and Gilead, the multinational company that subsequently took it over, spent approximately 60 million dollars between the development of the molecule and the pre-clinical and clinical trials. The only way to recover the costs is to increase the selling price; however, this makes the drug inaccessible to many patients, with the risk of the drug remaining unsold. In some countries Gilead has given permission to other companies to produce the drug, although it is still patent-protected, thus promoting its consumption in India, where a course of treatment can be purchased for 400 dollars.
Then Dr. Massimo Pellegrini from the University of Modena and Reggio Emilia, who was in charge of the organisation of the clinical trial based on the low-protein diet carried out in 2011, illustrates the most important results, published in the scientific review Autophagy a few weeks ago. Dr. Pellegrini shows
how a low-protein diet, followed by 7 patients for one year, proved to be not only harmless, but also effective in reactivating autophagy, the system whereby the muscle cells set in motion a self-cleaning process and eliminate damaged components, a process which is deficient in muscles lacking in Collagen 6. Data show that this diet is conducive to a decrease in cell death and to an improvement in the function of the mitochondria, the organelles responsible for energy production in the cells, which seem to be altered in Bethlem e Ullrich patients. Dr. Pellegrini then goes on to describe the characteristics of different types of diet, not only of the low-protein diet, and explains which diets in particular can be exploited to reactivate autophagy, focusing mainly on foods containing greater quantities of spermidine, a substance which, in Collagen 6 deficient mice, has the power to reactivate autophagy and to produce a series of beneficial effects on muscles, including a lower cell death rate and an improvement in mitochondrial function.
Finally Leonardo Baldinu, President of UILDM (Italian Union for the Fight against Muscular Dystrophy) intervenes. He begins by congratulating Cecilia and all the other members of col6.it on having succeeded in forming a small, but active and compact group, constantly on the increase.
Leonardo also commends the Group on its efforts to organize on a regular basis these meetings, which are not only useful to the patients, but also to the doctors and researchers themselves, because they offer patients the opportunity to discover, understand and appreciate the people who are working and studying on their behalf. Pointing out that col6.it forms part of UILDM, Leonardo draws our attention to the various ways in which the group can actively participate in the community. Indeed, the condition of patients affected by muscular dystrophy in Italy can be hugely improved if we work continuously to improve barrier-free accessibility and to guarantee certain fundamental rights, including education up to University level, guarantee of employment and the attainment of as independent a life as possible. Only by defending these rights can we envisage a considerable improvement in patients’ living conditions, at the same time enabling them to contribute to the development of society.
After the lunch break, we are shown a video-message from Telethon. Anna Ambrosini, who is responsible for the Telethon Scientific Committee research programmes, sends us her greetings and assures all the members of the col6.it Group of her support, as well as of Telethon’s goodwill towards the doctors and researchers involved in the study of Collagen VI linked pathologies. Alessia Daturi, who is in charge of the Associazioni Amiche (Friendly Associations) network, namely those associations of patients that accompany Telethon in the battle against genetic disorders, takes over from Anna Ambrosini. Alessia assures us of her willingness to act as a link between patients and the communication team of the Telethon marathon. Then she goes on to explain that, for this purpose, the presence of voluntary spokespersons talking about their life and medical history, via the social or other media, would be indispensable. Alessia concludes her video-message with an invitation to attend the next Friendly Associations conference, to be held on 13th and 14th March in Riva del Garda, with the participation of over 180 associations together with researchers, who aim to inform patients of the progress made to date in the field of research.
At the end of the proceedings, there is a fruitful moment of discussion, during which patients have the possibility to ask doctors and researchers a series of questions: in this way, various topics are addressed, such as funding for research, future clinical trial projects, ways in which to enhance the profile of the Group, as well as other issues.
This meeting, like other previous meetings, proved to be an excellent opportunity for the exchange of information, advice, opinions and explanations. We are fully confident that we are moving in the right direction and that future meetings will prove to be more and more profitable and will further the growth and consolidation of the col6.it Group.