In the middle of the sixties of the twentieth century Enno Mandema, professor of medicine in Groningen, became interested in the field of amyloidosis. Together with the internist Jan Scholten and the biochemist Luuk Ruinen he started investigating this disease. Soon he came into contact with the American researcher and professor of medicine Alan Cohen. Together they organised the first International Symposium on Amyloidosis in Groningen (1). This was a success and became a new tradition. Symposia were held since that time in different places all ove the world. The last symposium was held in Tours (France) in April 2004 and the next, eleventh, symposium will be held in Woods Hole, Massachusetts (USA) in November 2006.
In the eighties Martin van Rijswijk (2), professor of rheumatology, became involved in this field of research together with the immunologically interested biochemists Jan Marrink and professor Pieter Limburg and the internist Sven Janssen (3). An international course on amyloidosis was organised in Groningen on the occasion of the retirement of Enno Mandema as professor in Medicine on 10 and 11 October 1986 (4). Since the end of the eighties the reumatologist Bouke Hazenberg has carried the torch of amyloid research, strongly supported by the research analyst Johan Bijzet. Limburg and Van Rijswijk are still involved, as well as many other people such as internist-rheumatologists Ingrid van Gameren and Reinhard Bos, professor of haematology Edo Vellenga, internist Els Haagsma, nephrologist Ron Gansevoort, professor of neurology Jan Kuks, professor of surgery Maarten Slooff, internists Andries Smit and An Reyners (5), professor of nuclear medicine Pieter Jager, and otolaryngologist Freek Dikkers. Collaboration also takes place in the field of pathology and clinical genetics.
During this period diagnosis and treatment of patients with amyloidosis reflected similar developments as seen in the rest of the world. Diagnosis improved, resulting in a good classification of the different types of systemic amyloidosis. A further refinement of diagnostic techniques has improved the accuracy of typing in individual cases.
After classification of the various types of amyloidosis research was aimed at finding the building bricks of amyloid deposits. The different precursor proteins were detected and techniques were developed to detect these precursor proteins routinely in the individual patient at diagnosis and during follow-up. Genetical research has made it possible to analyse DNA in families and to show specific mutations related to the development of amyloidosis.
More knowledge of the background of different types of amyloidosis resulted gradually in a shift of the clinical research into the direction of the most important aspect of the disease, i.e. therapy. Identification of the precursor proteins has drawn the attention to stop ongoing production of these proteins. Chemotherapy appeared to be useful for the treatment of AL amyloidosis and liver transplantation for the treatment of some familal forms of ATTR amyloidosis. The best way to treat AA amyloidosis is a complete cure of the underlying inflammatory disease. A new development in AA amyloidosis is the introduction of Fibrillex™, a so-called GAG-mimetic drug. This drug has been developed specifically to inhibit deposition of AA amyloid. If this drug appears to be effective in AA amyloidosis, similar drugs may be developed in the other types of systemic and localised amyloidosis.
During treatment of amyloidosis it became clear that instuments needed to be developed to measure the effect of therapy on the amyloid load. In the beginning of the nineties Pepys and Hawkins developed SAP scintigraphy for this purpose. This SAP scan has been introduced also in Groningen. Although the scan is not always informative in every patient and every type of amyloidosis, the value of the SAP scan is great in many individual cases. Involvement of organs such as liver and spleen can be visualised as well as the course of the disease during therapy. Unfortunately the scan does not help to show involvement of heart and nerves.
So, in short some developments in the field of amyloidosis have been presented. We expect new therapeutical developments in the next years, however, progress will be slow and efforts of patients and doctors will be high. As clinicians in Groningen we hope that it will become possible to develop highly effective and above all safe drugs to stop further accumulation (and possibly complete disappearance) of amyloid in all patients with amyloidosis.
1. Enno Mandema, Luuk Ruinen, Jan H. Scholten en Alan S. Cohen. Amyloidosis. Proceedings of the first Intenational symposium on amyloidosis, University of Groningen, 1967.
2. Martin H. van Rijswijk. Amyloidosis. Thesis, University of Groningen, 1981.
3. Sven Janssen. Clinical and diagnostic features of amyloidosis. Thesis, University of Groningen, 1985.
4. Jan Marrink en Martin H. van Rijswijk. Amyloidosis. International course, University of Groningen, 1986.
5. An K.L. Oei-Reyners. Cardiovascular autonomic function tests: methodological considerations and clinical aspects. Thesis, University of Groningen, 2002.