Some diseases are so rare that only sufferers or specialists know about them. Patients with diseases that affect a significantly smaller percentage of the population than diabetes or Alzheimer’s disease are battling alongside medical doctors and scientists to encourage wider interest in these rare diseases from the public, the pharmaceutical industry and government. An international conference on rare diseases was held in Freiburg (Germany) in February 2012, where BIOPRO Baden-Württemberg talked with Prof. Dr. Bodo Grimbacher, director of the Centre of Chronic Immunodeficiency (CCI) in Freiburg, and Prof. Dr. Maximilian Muenke, paediatrician and human geneticist from the National Human Genome Research Institute (NHGRI) in the USA. Read in the second part of the interview why society should at large be interested in orphan diseases.
Muenke: First of all, we have to consider the people who suffer from these diseases. We need to gain insights that help us diagnose their particular disease and find therapies for treating them. From a practical point of view, being able to diagnose a child very early on, in the case of either common or rare diseases, is very beneficial for society. Apart from anything else, it makes economic sense. Let me give you an example of quite a well-known metabolic disorder: if parents know that their child has maple syrup urine disease, the child can be fed a specific diet with minimal levels of the amino acids leucine, isoleucine and valine in order to prevent neurological damage. Children afflicted with this disease can live healthy normal lives and this comes at very low cost, with money only needed to purchase specialised protein preparations containing the required amino acid substitutes. The early diagnosis of such diseases helps reduce suffering as well as the cost to health systems.Grimbacher: It is worth considering that the total number of rare diseases is quite high, even though each disease only affects a tiny percentage of the population. As previously mentioned, around 6,000 diseases are recognised as rare diseases. And 6,000 times one patient out of 200,000 is costly for the health system. These patients are very expensive, particularly because the diseases they have are so rare. The pharmaceutical industry cannot produce large quantities of medicines economically, the diseases in question are difficult to diagnose and are often only diagnosed at a very late stage, generating huge costs.Muenke: This is why for me it is so important that Germany has decided to focus more on rare diseases. The University of Freiburg was the first university in Germany to establish a Centre for Rare Diseases three years ago, Germany is home to the Eva Luise and Korst Köhler Foundation that awards prizes for research into rare diseases, and Germany was also one of the many countries that got together to create the Rare Disease Day on 29th February 2012. All this shows that a growing number of people in Germany consider it important to deal with rare diseases. And the same is happening in the USA. The NIH has an Officer for Rare Diseases, the NIH Clinical Center has launched the Undiagnosed Diseases Programme, which seeks to provide answers to patients with mysterious conditions that have long eluded diagnosis, cannot be treated and whose condition is declining. The success rate of diagnosing rare diseases can then be up to 50%. I have worked as geneticist for over 20 years; as a paediatrician I often meet patients with rare diseases. But rare diseases have long lacked recognition as a field that is worth investigating. In the past, a young researcher would never have been advised to focus on something that is rare. This attitude is gradually changing.
Grimbacher: The pharmaceutical industry is quite interested in rare diseases, at least in the field of immunology. However, it is not interested in individual patients but rather in what it can learn from this type of research. For example, my own research into people’s susceptibility to fungal infections clearly shows that it is possible to deduce basic pathogenetic mechanisms from the individual monogenetic defects of a specific family. And in my special case this means information on how the immune system controls fungal infections, what is important and what is less important. The pharmaceutical industry is quite interested in fungal infections. It is a huge market, which is why the pharmaceutical industry wants to learn from these monogenetic diseases and find out whether it will be possible to develop drugs that are able to interfere with the relevant signalling networks we’ve identified with monogenetic diseases and that are also of relevance for more common diseases. This is not particularly altruistic, but the result is nevertheless positive. One can kill two birds with one stone if one uses the interest of the pharmaceutical industry in rare diseases to help a large number of people who suffer from common diseases.
Muenke: Oh yes, definitely. Our research shows how the development of the brain comes apart at the seams, and how these children suffer from severe mental retardation. This research also gives us insights into normal brain development. We already have a much better understanding of the functions of the genes and molecular signalling networks involved. For example, we have been able to show that one of the major genes – called sonic hedgehog – is extremely important. The gene product must be covalently bound to cholesterol in order for specific developmental steps to progress normally. For example, this rare disease has shown us that many women with a low cholesterol level during pregnancy give birth prematurely. The babies are also born underweight. As a paediatrician, I am of course very pleased that I have discovered something that is somehow related to premature birth, which is associated with problems and is also a relatively frequent occurrence. It is always the same with basic research. You never know whether you will discover key knowledge by focusing on something that initially appears to be quite exotic.
Bodo Grimbacher studied medicine at the Aachen University of Applied Sciences and the University of Freiburg between 1988 and 1995. He did his doctorate in the Department of Rheumatology and Clinical Immunology at the Freiburg University Medical Centre, and subsequently spent a postdoctoral period at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) in Bethesda/USA from 1997 to 2000. He was lecturer and Emmy Noether research group leader in the Department of Rheumatology and Clinical Immunology at the Freiburg Medical Centre from 2000 to 2006, and habilitated in the field of immunology in 2006. He then became head of a Marie Curie research group in the Department of Immunology at the Royal Free Hospital and the University College in London. He has been scientific director of the Centre of Chronic Immunodeficiency (CCI) in Freiburg since 2011. Grimbacher investigates the genetic causes and molecular pathology of immune system diseases.Maximilian Muenke finished his medical studies at Freie Universität Berlin in 1979, and did his doctorate in human genetics with a special focus on paediatrics. Between 1980 and 1990, he focused on human genetics research at the University of Kiel, Yale University in New Haven/USA and at the Children’s Hospital and University of Philadelphia/USA. He was professor at the University of Philadelphia in the Department of Human Genetics and Molecular Biology between 1990 and 1997 and was then appointed head of the Section of Human Development in the Department of Human Genetics of the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) in Bethesda/USA; in 2000, Muenke became director of the NHGRI's Department of Human Genetics. He is particularly focused on genetic nervous system disorders in children, some of which have a very low incidence, and the molecular mechanisms and genetics of brain development.
Further information:Prof. Dr. Bodo GrimbacherScientific DirectorFreiburg University Medical CentreCCI - Centre of Chronic ImmunodeficiencyEngesserstr. 4 79108 FreiburgTel.: +49 (0)761/ 270 - 77731Prof. Dr. Maximilian MuenkeNational Human Genome Research InstituteNational Institutes of Health35 Convent Drive, Building 35Bethesda, MD 20892-3717Tel.: +1-301-402-8167FAX: +1-301-496-7184E-mail: mamuenke(at)mail.nih.govWeb: www.genome.gov/Staff/Muenke