Thanks to the invaluable collaboration of Dr. Martina Chrisam from Prof. Bonaldo’s laboratory, we are now publishing the report of the third group meeting of the Collagen VI Italy group, held on 18 June 2016 in Bologna. The report details the topics addressed during the day by doctors and researchers. As the report shows, the Collagen VI Italy group meetings are increasingly becoming occasions for consolidating collaboration and exchange between the scientific world and that of patients and their families. Only together can we walk the path towards defeating these diseases!
United in col6.it, because together we can do more!
Report of the third group meeting of the col6.it group – 18 June 2016 c/o Centro Sociale Ricreativo e Culturale A. Montanari in Via di Saliceto, 3/21, 40128 Bologna. The key word is ‘together’ because patients, doctors and researchers together can really shape a new reality, in which the quality of life and awareness of patients will be significantly improved.
Cecilia Sorpilli, the promoter and soul of col6.it, opens the day by giving us a few updates on the status of the group: the confluence within UILDM has now been fully completed and, through the website www.col6.it and the Facebook page, the visibility of the group is slowly increasing.
This is of paramount importance to enable more patients with Bethlem Myopathy and Ullrich Congenital Muscular Dystrophy to join our cause. The topics covered during the day ranged, as usual, from topics related to Collagen VI research to more strictly medical issues. In his opening speech, Prof. Paolo Bonaldo told us how it was possible to determine that Bethlem Myopathy and Ullrich Dystrophy are diseases due to defects in Collagen VI.
Towards the end of the 1980s, Prof. Bonaldo’s main interest was to understand how Collagen VI was made, and how cells were able to build it up and fix it in the extracellular environment. No information was known regarding the function of Collagen VI, nor was it thought to be in any way related to human disease. A key event, which represented a real turning point in this field of study, was the production of a mouse whose cells were unable to produce Collagen VI.
It was immediately obvious to Prof. Bonaldo and his co-researchers at the time that this mouse had some kind of muscular problem and, through studies conducted by geneticists and neuromuscular clinicians, it was possible to verify that a Collagen VI deficiency was present in certain patients with similar muscular problems.
Doctors and researchers together succeeded for the first time in informing Bethlem patients as to the cause of their condition: Collagen VI deficiency. This discovery, published in 1996, was followed in 2001 by the discovery that Ullrich Dystrophy is also linked to Collagen VI deficiency. In these two decades, mice lacking Collagen VI have enabled us to make enormous advances in our knowledge of the functions that this protein performs.
The challenge now is to understand what the connection is between the alteration of the matrix, which lies outside the cell, and the abnormalities observed within the cell: reduced cleansing activity (a process called autophagy), and the poor functionality of the cell’s energy stations (i.e. the mitochondria). The lack of funding that plagues Italian research makes the challenge more difficult, but Prof. Bonaldo is determined and confident of finding the answers and the necessary funds. Prof. Bonaldo’s co-researchers subsequently updated us on the latest developments in Collagen VI research. Dr. Silvia Castagnaro briefly outlined some of the analyses conducted as part of the clinical trial based on the low-protein diet, the results of which are currently being published and will therefore soon be made known to the world scientific community. Dr. Martina Chrisam, on the other hand, illustrated the beneficial effects of spermidine on muscle pathology in mice lacking Collagen VI, presenting some of the recently published data. This study represents a starting point for formulating a new therapeutic possibility for patients. Prof. Luciano Merlini then brought to our attention a topic that bridges the gap between clinics and research: the difficulties associated with clinical trials to test effective drugs in the treatment of rare diseases. Indeed, past experience has taught us that it is very difficult to convince the scientific community of the efficacy of a treatment on Bethlem and Ullrich patients, because the number of suitable patients that can be collected in a single clinical trial is generally very low, given the rarity of these pathologies. This is where Prof. Marco Viceconti, who heads a group at the University of Sheffield in the UK that deals with ‘in silico clinical trials’, was able to step in. But what is it all about? Silicon is the main component of computer chips; an ‘in silico clinical trial’ is a computer-simulated clinical trial in which patients are virtual and intricate mathematical calculations can predict the effects of the drug that is being studied on these virtual patients. These calculations must, however, be constructed on the basis of real data, so such work should also include an actual trial in which doctors and researchers can collect as many data as possible to hand over to Prof. Viceconti and his collaborators for the construction of the ‘super equation’. This strategy combining both clinic and computer is currently being applied in various areas of biomedical research, and we hope that it will soon prove useful also for research into rare diseases such as Collagen VI deficiency disorders.
Another insight into Collagen VI research was provided by Dr Patrizia Sabatelli, who had recently published two important papers describing alterations in the tendons in mice lacking Collagen VI and in cells isolated from the tendons of patients with Collagen VI deficiency. Tendons are the link between bones and muscles, and the presence of a defect in them supplements our knowledge of why patients suffer from movement difficulties. As well as telling us that muscle is not the only tissue we need to keep under control, it also leads us to consider the tendon as another target to focus on to improve patients’ motility. The day’s medical team was represented by Dr Andrea Fabiani, a pulmonologist, and Dr Mariada Perrone, an anaesthetist. Dr Fabiani explained in detail how we breathe, highlighting the importance of muscles in this process. In fact, the diaphragm and intercostal muscles are primarily involved in the expansion of the lungs that allows the introduction of oxygenated air during inhalation, and in the subsequent exhalation that enables their emptying. These movements also facilitate the escape of pathogenic bacteria that can lurk inside the lungs and become trapped in mucus. When the muscles function poorly, exhalation and even coughing are less effective and this increases the risk of contracting lung infections, because bacteria are not expelled to the oral cavity but remain in the lungs, where they can proliferate and give rise to an infection. Dr Perrone’s talk focused on the major complications, mainly respiratory, to which patients with Collagen VI deficiency are exposed.
Explanation was given as to the meaning of general anaesthesia, how important it is to maintain a balance between the components related to the respiratory system, respiratory muscles and tissue oxygenation. Through a video, we were shown how patient intubation takes place, a procedure which is necessary to ventilate and oxygenate a patient under general anaesthesia. In these patients, the intubation manoeuvre can be complex due to the problems of airway stiffness, related to the morphology of the airways, which may be anatomically different from patients without Collagen VI deficiency.
It is important to be well informed and to be constantly aware of the risks involved in surgery and the anaesthesia attached to it. Today, fortunately, there are alternative techniques to general anaesthesia and oxygenation monitoring systems that can be considered in the case of patients with this or other myopathies.