Professor Susanne Gerit Kircher of the Medical University of Vienna discusses the situation of rare diseases in Austria, including Mucopolysaccharide storage disorders.
In Europe, a rare disease is defined as a condition which affects fewer than one in 2,000 people (or five in 10,000). The EU, with a population of 513.5 million people in 2019, is home to an estimated 30 million people with one of the 5,000 to 8,000 known rare diseases. This means that in each Member State, only a handful of patients are affected with the same disorder. In Europe, as a result of its many countries, languages, different health insurance systems, and the many ways of caring and treating those individuals with their special needs, it is difficult to form a comprehensive overview.
In 2008 the European Commission produced a communication to the European Parliament, the Council of the EU, the European Economic and Social Committee and the Committee of the Regions; saying: “The specificities of rare diseases – limited number of patients and scarcity of knowledge and expertise – single them out as a distinctive domain of very high European added-value. European cooperation can help to ensure that scare knowledge can be shared and resources combined as efficiently as possible, in order to tackle rare diseases effectively across the EU as a whole”.
The need to get active was clear in 2008; and that need is still present in 2019. The landscape for each of these orphan diseases is opaque; and while each individual rare disease only affects a few patients in each Member State, in total more than 5% of the EU’s inhabitants are affected. These patients must fight for a correct diagnosis, for an adequate therapy and enough support from the community, for specialists and hospitals informed about their diseases, to be noticed and treated specifically as a patient affected by a rare disease.
The situation for MPS patients
Mucopolysaccharidoses are a group of these rare diseases. They are inherited disorders with increasing storage in the lysosomes due to insufficiently working lysosomal enzymes. These enzymes are necessary for the regular breakdown of glycosaminoglycans (GAGs) in the connective tissue, cartilage and bone. This is a breakdown which is necessary for the exchange of damaged structures and renewing processes. These tissues have different characteristics and different GAG-components, meaning that the composition of each tissue is different. The wide range of involved enzymes is reflected in a group of 11 enzymes, each of which is a different gene product of another responsible gene.
The fact that the rare mucopolysaccharide storage disorders can be caused by 11 different enzymes, each of them with different consequences, causes a division into 11 different MPS subtypes; each of which occurs with an ultra-rare frequency or may not even have yet been observed in Austria. For instance, MPS IX was never diagnosed in Austria until now; while MPS VII has only been identified once in 30 years. The very rare situation of a female patient affected by MPS II type has only been seen once.
To concentrate that minimal knowledge, a group of patients and families affected by MPS was founded in Austria more than thirty years ago. The first meeting and exchange of information about the diseases was held in 1987 on the border between Germany and Switzerland, to give families from both those countries the chance to take part. In the following years, families and patients from an increasing number of neighbouring European countries came to the annual meetings and conferences. Researchers, medical doctors, caregivers, all met to exchange knowledge and learn from each other.
MPS Europe and around the world
In 2016, MPS Europe GmbH was established by the national MPS societies of 12 European countries, including Austria, Denmark, Germany, Ireland, Italy, Hungary, Netherlands, Serbia, Spain, Sweden, Switzerland and the UK. Its headquarters are based in Aschaffenburg, Germany. The initiative started from Austria and Germany, the first and the second MPS society existing in Central Europe, both starting more than thirty years ago. The number of other national MPS societies in this alliance is continuously increasing and it is the hope to get the same strength as similar umbrella organisations in the United States, in the Asian-Pacific region (Japan, South Korea, Australia) and the newest group based on the South American continent.
The challenges observed on national level are the same within the European Union and neighbouring third countries: lack of access to early diagnoses, adequate therapy and treatment is a fact which must be changed. What cannot be altered on a national level has the potential to be solved on the European level. The aim to gather national societies and advocate for all MPS patients in Europe should help to offer the same level of medical care and treatment for affected patients in all member states.
This is, in fact, not at all the case. There are countries which do not offer any of the available enzyme replacement therapies. Other countries do not have the opportunity to operate the cranio-cervical junction in the case of instability and an impending tetraplegia. Again, other national health systems do not offer the hematopoietic stem cell therapies, despite these being the best treatment for very young MPS I patients.
In the beginning of the 1990s, the first International Symposium about MPS and Related Disorders was held in Manchester (UK), followed by Essen (Germany), Wollongong (Australia) and Vienna (Austria). This was the beginning of intensive communication between physicians, scientists, patients and their families and representatives of other existing MPS societies.
MPS patient registries
Nowadays, established international MPS patient registries represent thousands of patients for each of the main MPS types worldwide. This makes the diseases and their natural history of the different subtypes, as well as the range of therapeutic procedures, visible. Knowledge has increased exponentially, as the observations helped to understand what MPS is, how it affects the patient; and how a can patient benefit from any therapy by comparison to those not treated.
However, there is another side to this. Most of these patient registries were created by pharmaceutical companies in order to increase the market for their products. With the era of enzyme replacement therapies, the collection of patients’ data was essential in order to calculate the financial risks for the development of any treatment, to find sponsors and investors. The rare disease treatment business is experiencing an unbroken boom.
The costs for any patient registry are not covered, not by the government or by the health- authorities. So far, only one independent register for MPS (MPS IVB) was established in Canada. The impressive value of data for research and future therapeutic strategies are not fully available to independent academic groups. All basic research on the development of therapies to market is no longer at universities, although most of the innovations originated at the universities. Unfortunately, it is not common in most cases that money flows back to the universities for their basic research.
The visible sign that MPS is existing all over the world is celebrated by the worldwide MPS Day on 15 May each year, with many local, national and international events for raising awareness. The preferred main colour chosen is blue. In Austria, local charity events draw attention to MPS and improve awareness for this rare disorder.
MPS: only one of the many rare diseases
The group of mucopolysaccharidoses represents one out of around 5,000 to 8,000 genetically caused rare diseases. The same fate meets all the others suffering from such an orphan disease, too. In Austria, we have 400,000 persons suffering from a rare disease; each of them with parents, a family, friends, and/or colleagues. More than a million people in Austria are directly confronted with the consequences of a rare disease, with missing knowledge, unknown expertise, not sufficient possibilities for diagnoses or adequate treatment. This means that as a result, there are no special places in kindergarten, schools, educations, or in professional lives. Therefore, there is also no suitable options for transport, or considerations for the special needs of these persons. If anything, there is help for everyone, whether it fits individually or not. This is not the way to have a quality of life, but one must be grateful and content, in the rich country of Austria, which has one of the best medical supplies. The situation is much more difficult in the Eastern and Southern countries of the European Union.
Rare diseases in Austria are each rare, but the problems to be solved are often the same. Thus, it is then not surprising that several groups representing another rare disease co-founded an umbrella organisation, the ‘ProRareAustria’ society, in 2011. This proactive alliance for rare disease represents around 70 different groups with a rare disorder and is the mouthpiece to be the partner for those affected and public relations, health and political contacts, as well as pharmaceutical companies, educational institutions and healthcare providers. They make the rare diseases visible and increase knowledge and understanding, as well as promoting the networking of individuals with a rare disease among themselves. Each year, there are local and national activities around 29 February. This symbolic date underlines the role of patients and their families with a rare disease: it does not really exist, only sometimes, under special circumstances. All groups in Austria meet at the Annual General Meeting and at the National Conference for Rare Disease.
National Action Plan for Rare Disease
ProRareAustria supports the National Action Plan for Rare Disease with expertise and experience. The focus is to show the social and structural deficits and to provide data and specific information about rare diseases to the policymakers. Some of the members are also part of EUPATI Austria, a platform and network to train and educate patients and patients groups to be equal partners for research and pharmaceutical industry.
“To put in place intersectoral action national plans for rare diseases in the member states” was one of the declared points of the European Commission. If necessary, this could be in the form of a collaboration across member states in order to share and co-ordinate expertise and information. These networks should foster research on rare diseases, including cross-border co-operation and collaboration to maximise the potential of scientific resources across the EU.
In March 2017, 24 European Reference Networks (ERNs) were launched with the aim to improve the care for these patients through cross-border healthcare. The aim is that medical knowledge and expertise travels across borders, rather than only between patients and experts. In 2018, 300 hospitals and 900 highly specialised teams from 25 European member states were participating and approved ERNs. In Austria, a few National Centres of Expertise or Excellence were also approved: for Epidermolysis bullosa, cancer in children; and for rare skin dermatoses. The number is steadily increasing; all metabolic laboratories from the Medical Universities have been accredited to have the best methods for the diagnosis of congenital metabolic diseases. As positive as these developments are, it is necessary to remember that there are 5000 to 8000 orphan diseases, most of which need special diagnostic procedures.
There were points considered and offered by the European Commission, including that the basis is an International Classification and Codification of these many known rare diseases, and the building of an Orphanet database, which is freely available to everybody. This should “tackle some of the main causes of neglecting the issue of rare diseases including the ignorance of which diseases are rare”.
MPS Society Austria and MPS therapy week
MPS Society Austria began as a patient representative organisation in 1984. Since this time, many things have improved, but there is still much to do. Since 2002, annual therapy weeks have brought together all those affected and their families to spend one week together; a week with a lot of therapies and units, but also a week with recreation, leisure and exchange of information. This time offers the possibilities to hear about the problems in the daily life, on social, medical, caring, educational, and professional levels. This information forms the basis to see were the problems are and to act as the patient advocacy. This includes problems with health insurance companies, authorities, tax office, federal social office, mobility, and everyday school life.
Problems are also on the personal level, with partners, not-affected family members; misunderstandings, fears and depression. On the one hand, the society is struggling to improve the situation, whereas on the other hand, the week with recreation, distance to the daily life and the experiences and strategies from others in a similar situation, can help to empower the presents. For several years, holiday weeks for the healthy sisters and brothers are organised, free from family and the burden of a sick sister or brother. Now, also weekends for mothers and separate from that also for fathers with MPS children are offered. MPS is a chronic disease but involves the whole family. This fact is true but unfortunately, not realised in any health system.
Are we finished yet?
Mucopolysaccharidoses in Austria have a rather good lobby and strong people representing the group of MPS patients. The power to change certain things came from the drive of leaders who either had or have had children themselves. MPS is a very serious disease and fatal without therapy, resulting in children living a few years or until puberty. This creates a very strong pressure to see improvement in certain areas. The key therapies have been realised with the help of the patients themselves or their patient organisations.
The first pharmaceutical company for enzyme replacement therapy was found through a tender issued by an Austrian university, which designed the technical prototype for the cell culture production machine. Several patient organisations have strongly supported the research that therapies now can be offered, even though they are so rare. But for many of the thousands of rare diseases, affected or their families and organisations are not as strong.
The EU’s 2008 guidelines are clear and well considered, but there is still a lack of implementation. There are no consequences for those states that are currently not doing enough for rare diseases. There may not be enough money for them if they cannot do it on their own, however it should still shake us awake: 2008 to 2019 is a period of 11 years, almost half a generation; and, for many people already affected, the end of their short life.
Austrian MPS Society