Today we are celebrating the X Day dedicated to rare diseases under the slogan “With the research the possibilities are infinite”. An effort at the service of all who spend themselves to assist and help those who are suffering from these diseases and their families, often devastated by very heavy situations. We talk about it with Professor Bruno Dallapiccola, geneticist, scientific director of the Hospital Bambino Gesù of Rome, and great expert of the sector.
Professor, what is meant for rare diseases and orphan drugs?
“Rare diseases are, in accordance with a definition accepted throughout Europe, those which have a frequency lower than one case every 2000 people. The point is that given the wide variety of these diseases which are about 8000, in Italy there is at least one million people suffering from these diseases, and it is a number rounded downwards, without counting the over 900,000 patients suffering from rare cancers. The estimates in the world are of 1 patient every 20 people. Orphan drugs are those used in the treatment of these cases. Fortunately the rare diseases patients do not rely just in this kind of drugs. Those currently authorized are around eighty while we have powerful tools for the treatment: at least 400 traditional molecules as well as rehabilitation, speech therapy, surgery, psychomotor, cellular and dietary therapy “.
Why is it important to emphasize this theme? What has it done up to now the Hospital Bambino Gesù, even though rare diseases do not affect only the children?
“No, of course, these are pathologies which traverse the entire population. Children are about 60% of rare diseases patients. Obviously for their characteristics, they are those that arouse more tenderness: in front of a congenital defect or a disease contracted in the early months or years of life, there is a much higher level of torment. The importance of this day is linked to the fact that we are talking about a topic that is penalized by the adjective that qualifies it. The concept of rare defines very well the frequency of the illness but not the dramatic problems around it. First of all its social dimension; the great loneliness; the problems faced by these people who daily struggle to find experts or to have the diagnosis of diseases that have devastating consequences. It is needed to draw the attention of the citizens on an issue that affects a very important part of the population. Before speaking of the Bambino Gesù, I would like to speak about what the country has done, because Italy has moved on this topic with the first national plan since 1998/2000, and in 2001 has made an extraordinary breakthrough with the creation of the national network of rare diseases and the exemption of the ticket on health services and drugs for the patients. This work, even if it has been carried on with inhomogeneous criteria by the Regions, has meant that today we have a national network of 196 hospital units, which in Europe are called Centres of reference for rare diseases, which are unique in the continent; only France has a structure similar to the Italian one. It is now clear that precisely for the peculiar characteristics, rare diseases need a multidisciplinary approach. At the Bambino Gesù we have 40 paediatric sub specializations. We are a centre of excellence, of reference, to the point that the largest Italian case histories, and one of the largest in Europe, of paediatric rare patients is of our Hospital. We also have the advantage of having the possibility to combine large clinical expertise with all the necessary tools and the laboratories. Let us not forget that 90% of these diseases are genetic and that one patient on 3 has not a diagnosis: often using genomic techniques we can find it”.
The portal Orphanet is a reference for people struggling with rare diseases. The numbers are impressive, with an average of 92,000 pages visited daily. How was it conceived? What are these data and what is the significance of this portal?
“The portal was born at the end of the nineties in France, created by Ségolène Aymé that after a couple of years realized that it could have been of European importance. We were among the first to be contacted. We knew each other for some time and she asked me if I wanted to manage the Italian interface of the portal. Even the portals in Spanish, English and German started almost immediately. Today for the amount of data treated, Italy is second only to France. One of the important aspects is the specificity of the portal because it is possible to know who does clinical activity in each country, who does research, what are the associations of support, what are the laboratories that do genetic testing. The access is free and is written in an extremely simple language, easily accessible by all. Another important thing is the creation of Orphacode, a coding system of rare diseases now accepted in many parts of the world (in Italy it is adopted by the Veneto and by other nine affiliated Region) that offers a series of advantages with respect to the codes previously used, that are now obsolete”.
The research in this field is vital but is it properly supported?
“It is a quite sour note because against the extraordinary results obtained in Italy, leader country in the research, funding are few. There is then an important chapter, started a few years ago and unlocked in December last year after a period of standstill: the found of the independent clinical research managed by the Aifa, powered by a specific amount deriving from the sale of drugs. There are then the fund raising, as Telethon, or European tenders and projects, but if we put all this in relation to the needs of the research, which goes from the epidemiological one, to the one on drugs, to the biological, social and economic aspects of rare diseases, and to the number of pathologies, actually the amount is rather poor”.
At the Bambino Gesù you have also established a clinic for undiagnosed rare diseases: What is it? Why have you decided to invest in this initiative?
It is the Columbus’s egg for a great general hospital as ours. Initially a clinic is a type of a virtual structure, because an undiagnosed disease passes through all the specializations and I cannot have 40 professionals who are waiting for the first patient who enters. We stimulate patients to send us a preliminary information via internet or e-mail in which they tell us: ‘My son has a heart disease and a mental retardation’. We implement the program so that the day that the patient comes to us, he will be visited by the neurologist and by the cardiologist. After that the patient enters a path, each one with a ‘case manager’ that follows him. Every week we have a ‘brain storming’, with an average of about twenty specialists who discuss and deal with the cases without diagnoses of the recent days. Sometimes we reach a diagnostic hypothesis, otherwise we call the patient and we do the analysis of the exome, of the 2 % of genes encoding. In this way in 42% of the cases we give a name to the disease. This exam is so important that in a document sent in December to the Health Council we have recommended that in the few centres that have the skills, this may be offered as a service because to analyse the patient and the parents costs today 2500 euro (probably in a couple of years it will cost a thousand) while a patient without diagnosis that runs around Italy costs a lot of money to the family and to the State. The equipment are not expensive, ranging from 200,000 to 600,000 euro. The difficulty is in the interpretation of the results. We shall centralize these tests, as it has been done in other countries such as France. It is not necessary that every region has his own laboratory. We need to unite more Regions in consortia, avoiding a plethora of technological platforms that often are not used. In Italy, there are already 5 centres for these analyses. It would be sufficient to implement them or to open maximum two more”.
The next 9 March in Vilnius will start the project of the European reference networks for rare diseases. How is it structured? What benefits will derive from it?
“At the moment these are 23-24 networks that start with a number of participants that varies from a minimum of 10-15 up to 90. Altogether are involved approximately 1000 centres and 350 hospitals. Italy has more than 50 hospitals and 200 Centres selected. These are networks with health care vocation but also with large research components. Considering the actual situation in Italy, I do not believe that we will have great advantages for the diagnostics, because we have all the necessary facilities. In the long term however there will be a benefit which in my opinion is represented by international sharing of case studies and research, also pharmacological. The Achilles’ heel of the system is that we create mega networks without money, each one with 200,000 euros that are sufficient only for the bureaucratic and administrative part. If there will be no parallel investment I fear that they will remain useless. A commitment of Europe in this field would be necessary but at the moment, unfortunately, I do not see it”.