How is MPS Austria improving understanding of mucopolysaccharidoses?

How is MPS Austria improving understanding of mucopolysaccharidoses?

Professor Dr Dr Susanne Gerit Kircher discusses her work alongside the Austrian MPS Society towards a better understanding of mucopolysaccharidoses.

Speaking to Health Europa during MPS Austria Therapy Week, Professor Dr Dr Susanne Gerit Kircher, of the Medical University of Vienna, discusses her work to improve understanding of mucopolysaccharidoses (MPS), a group of rare lysosomal diseases; the progress that has been made in clinical research and diagnostics; and the history of the Austrian MPS Society.

How closely do you work with the Austrian MPS Society? How does the work of the society inform your own research priorities?

In 1984, I met the first family with a child suffering from mucopolysaccharidoses. Diagnosis at that time was already known, but no cure existed. The family tried every form of possible therapy, hoping to improve the condition of the daughter. Barbara was three years old. The parents prepared a special diet of powder produced by Nestle, giving her the yeast of beer with enzymes. My role was to meet the mother, Marion Kraft, and daughter very often to investigate Barbara’s urine to see if I could see any positive effect or benefit. At this time every week had its ups and downs for the family and they were disappointed to hear that there was no real cure. During these months, I answered many questions for the family that nobody else answered. I myself had only a vague idea about the disease, but I informed myself and, from that time on, other medical doctors and nurses who did not know much about the disease.

My work at the Institute of Medical Chemistry at the Medical University of Vienna was to make urine the first step when screening for a diagnosis of mucopolysaccharidoses. Because any further diagnostic procedures were very complicated and often not available in Austria, my investigations showed if any further diagnostic procedures were necessary or not. For me, my work had the purpose of telling the doctors and families: yes, it is MPS or no, it is not MPS. To make this diagnosis without the option of a cure was frustrating. Everybody wanted to me to tell them the prognosis, the prospects for life, anything. But my level of knowledge was the same as all clinicians’. Information and to accompany the families for years was the only thing I could offer.

There were similar disorders and I increased the spectrum of diseases I could recognise with the urinary screening. I thought that if I have difficulty finding the specific signs they show, how difficult must it be for clinicians who never have even heard of the disease? For this reason, I had visits and studies in the Institute of Child Health in Great Ormond Street Hospital in London, in Mainz, in the Children’s Hospital of Manchester, and in Hamburg. This was because MPS has some differential diagnoses from the spectrum of lysosomal disorders. All strange-looking patients were thought to suffer from MPS, but nobody had ever heard of other very similar disorders, for instance mucolipidosis, fucosidosis or mannosidosis.

When I visited London for the first time, I met Christine Lavery, another mother of an MPS child. She told me that there were several families in the UK and they had had their first meeting with these families just before. She invited me to come to the next meeting. Coming back to Vienna, the Austrian mother told me that she was informed by a friend from South Africa that there was a group of families and patients in the UK. From that moment on it was clear that we should go together to the next English meeting. They called it a conference as they had some medical doctors giving lectures about MPS. After this conference we were sure to start our own Austrian group. This was in 1986. The first Austrian conference was in 1987, together with families from Austria, Germany and Switzerland. From each of these countries we got to know a couple of families. If I remember right, there were about 20 families. From that time on, I supported the group with any information I could find out, I made information sheets and booklets, and I went with the mother to hospitals, medical doctors and professionals to introduce MPS. This work has not stopped for the last 35 years.

Barbara died at the age of seven. From that time on, the family tried to find another family to continue the MPS group and, in 1999, Michaela Weigl and her family officially became the head of the Austrian Society. At that time, Michaela’s daughter Maria was very young. Michaela dedicated most of her efforts to finding a cure for her daughter, and any energy she had was put into reaching that goal. It became a reality in 2011 when Maria was included as one of the first patients for clinical trials for MSP IVA.

For decades, any medical question from the Austrian (and very often German) group was discussed with me and any projects they wanted to support agreed in consensus with me. From my side, I published literature about MPS, gave lectures, and moderated the Austrian (and often the German) conferences. We supported other countries in Europe to start their own MPS groups and, as a result, we can say that we helped to initiate such groups in Germany, Switzerland, Hungary, the Czech Republic, Croatia, Serbia, Italy, Romania and Russia. For at least the first meeting of their families, we visited their conferences and were open to any questions from medical professionals, carers and families.

At the same time, I continued with my investigations at the institute with the financial support of the Austrian group, because it was not the intention of the university to support this. When publishing about any aspects of mucopolysaccharidoses, such as living as an adult, daily life, pregnancies of MPS mothers and fathers and many other aspects, the Austrian MPS Society has always supported me with information and photos. I visited other MPS conferences in other countries together with the Austrian group and met numerous patients and gained much information about their life. I would say that this was a win-win situation for both sides, with each of us focused on the aim of improving the prospects for patients with MPS and their families.

What progress has been made with regard to clinical research and diagnostic tools in recent years?

Progress has been enormous in the field of mucopolysaccharidoses. During the last few years, there have been several improvements:

  • Genetic tests are very easily available;
  • Dried blood spots on filter paper cards can be sent easily to laboratories all over the world; and
  • Knowledge on MPS has increased a lot by collecting all clinical data in registries. Within those, information on hundreds of patients and data in patient registries can help us to understand the clinical history much better than from the experience of just a couple of patients.

In addition, in earlier times, urine samples and the measurement of enzyme activity was the way to diagnose mucopolysaccharidoses. In many cases it was necessary to make a skin biopsy to gain material which was cultivated in cell cultures for weeks. Getting a diagnosis took months. Even in cases of prenatal diagnosis it took weeks until a diagnosis was performed. In some case, the diagnosis of an affected pregnancy was made in the 24th or 28th week of pregnancy, which was traumatic for the pregnant woman.

More recent tests have improved the certainty of results, and a much shorter time is necessary for investigations. Genetic tests are very helpful, as the knowledge of a specific gene mutation in one family makes the diagnosis of other family members and relatives much easier – a foetus can be diagnosed within a few days. The specific gene mutation can also help in some ways to say more about prognosis. Severely affected patients often have stop-mutations and no enzyme activity at all, compared to attenuated forms with some small amount of enzyme activity due to missense mutation.

Diagnosis has changed in the mode of stepwise performance. In earlier times, clinical symptoms led to the investigation of urine samples. If they showed a pathologic result, the next step was to measure enzyme activity in the blood or skin fibroblasts. If the diagnosis was performed, genetic testing followed.

Nowadays, dried blood spots on filter paper cards are covered with the patient’s material and sent to international laboratories such as Centogene, and the results and genetic confirmation are performed within a few weeks. The material investigated is not necessarily the missing enzyme but so-called ‘biomarkers’, abnormal products found in the patient’s blood due to undegraded storage material. Research on biomarkers for MPS is still in progress but is promising. In a project performed by the Pediatric Department of the Medical University of Vienna, more than 30,000 filter paper cards from newborn screenings from the Austrian newborn screening were investigated for different treatable lysosomal diseases, including some of the MPS types, or Gaucher and Pompe disease. They could reveal also MPS patients.

What more needs to be done to develop a better understanding of the disease on the whole?

Learning more and more about mucopolysaccharidoses is one good way. An important aspect concerns the increasing knowledge about the natural history of several MPS types. The collection of data is going on for nearly all types. Unfortunately, some of the biggest registries (MPS I, II and IVA) for the treatable types were started when the clinical trials for the enzyme replacement therapies began. They were founded by the involved pharmaceutical companies and are in ‘their hands’. This means that any new publications were created in the time of clinical trials/soon after being accepted on the market. It is rather quiet now and, for me, it is not clear who is involved in these registries now and with which interests. Who would be interested in publishing about the success or perhaps not always success of the therapies etc.?

Also improving understanding of mucopolysaccharidoses is the wide-spread knowledge based on the internet, such as websites and Facebook. Most of the MPS groups offer up-to-date information on their homepages which is often more informative than medical books.

What are your thoughts on the Therapy Week event? What do you feel are its biggest benefits?

Therapy Week has always been the biggest event of the year for all patients, families, therapists and doctors.

In earlier times, it was because everybody wanted to be informed about the newest information about mucopolysaccharidoses, about any trials with animals, and later with patients, and about better care for different specific problems, such as nutrition, anaesthesia, heart and lung problems, orthopedic and ear-nose-throat difficulties, epilepsy, sleep disturbances, brain pressure, eye etc.

The Austrian MPS Society was the platform to be kept informed about the latest news. Conferences featured invited speakers from Austria and, every second year, international speakers. At this time the international working group was founded with one representative of each country recommended by each society and the medical doctor caring for the patients in that country. The conference now takes place only once every second year, but increasingly important is the Therapy Week, which boasts numerous therapy units and leisure time for patients and their families.

The way the Therapy Week has been organised has changed over the last 17 years. It is now eight days (including arrival and departure), and instead of the patients consuming therapies passively, there are more and more occasions to advise the parents on how to deal and manage with their children during the year at home, as well as the things they could do better in their daily lives to work actively on their health. There has been a shift from passive consumption to active and self-responsible patients. The exchange of strategies is perhaps more important than just knowledge about the disease.

Therapy Week for me is a ‘colourful’ time. It is a pleasure to see so many friends and a pleasure to see children developing into adulthood and developing individual personalities, but at the same time it is sad to see parents whose child has passed away and sad as well to see some of the patients becoming worse and losing their capabilities more and more each year.

But the personal interaction with all participants is the most important thing. The energy I get from that gives me enough motivation to work and publish the rest of the year. I am grateful that these patients and families have changed my personality, too, and made me much better prepared to face personal problems.

Professor Dr Dr Susanne Gerit Kircher
Medical University of Vienna

This article will appear in issue 6 of Health Europa Quarterly, which will be published in August.


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