Der Nephrologe

, Volume 10, Issue 3, pp 207–213 | Cite as

Enzymersatztherapie bei Morbus Fabry

Leitthema
First Online:
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Zusammenfassung

Hintergrund/Ziel

Morbus Fabry ist eine lysosomale Speichererkrankung, die durch eine Mutation im Gen für α-Galaktosidase A hervorgerufen und X-chromosomal vererbt wird. Es kommt zu einer verminderten oder fehlenden Funktion dieses Enzyms und dadurch zu einer Ablagerung von Glykosphingolipiden in allen Geweben des Körpers mit entsprechender Organdysfunktion. Unbehandelt beträgt die Lebenserwartung bei Männern mit M. Fabry im Durchschnitt 50 Jahre, bei Frauen 70 Jahre.

Material und Methoden

In Europa sind zur Enzymersatztherapie seit 2001 zwei Präparate zugelassen: Agalsidase alfa und Agalsidase beta. Beide Präparate unterscheiden sich in ihrer Herstellungsweise, Antigenität und in der bei jeder Infusion verabreichten Dosierung. Da die Therapiekosten sehr hoch sind und die Enzymersatztherapie chronisch durchgeführt wird, wurde 2013 eine AWMF-Leitlinie zur Diagnostik und Therapie des M. Fabry veröffentlicht, in der Kriterien definiert sind, wann eine Enzymersatztherapie begonnen werden sollte.

Ergebnisse

Eine Vielzahl von „Open-label“-Studien, unkontrollierten Studien sowie einige placebokontrollierte Studien und Auswertungen von Registerdaten konnten in den letzten Jahren eine Reduktion der neuropathischen Schmerzen, der gastrointestinalen Symptome, eine Verlangsamung der Nierenfunktionsverschlechterung, eine Reduktion der kardialen Beteiligung und eine Verbesserung der Lebensqualität unter der Enzymersatztherapie dokumentieren.

Diskussion

Ob jedoch das Überleben von Patienten mit dieser schweren Erkrankung verbessert wird und ob Unterschiede zwischen beiden Enzympräparaten bezüglich klinischer Endpunkte wie Herzinsuffizienz, Nierenversagen, Schlaganfall oder Tod bestehen, ist bisher noch nicht bekannt.

Schlüsselwörter

Morbus Fabry Enzymersatztherapie α-Galaktosidase A Agalsidase alfa Agalsidase beta 

Enzyme replacement therapy in Fabry disease

Abstract

Background/objectives

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding alpha-galactosidase A, an enzyme involved in lipid metabolism. The activity of alpha-galactosidase is reduced or lacking in Fabry disease leading to accumulation of glycosphingolipids in virtually all organs of the human body and to progressive organ dysfunction. Without enzyme replacement, the average life expectancy is limited to 50 years in men and to 70 years in women.

Material and methods

In Europe two different enzyme preparations, agalsidase alfa and agalsidase beta, are approved for the treatment of Fabry disease. Both compounds differ in the manufacturing process, the antigenicity and dosing. Enzyme replacement therapy (ERT) is costly; therefore, in 2013 the Association of the Scientific Medical Societies in Germany (AWMF) published guidelines for diagnosis and therapy of Fabry disease defining criteria for when ERT should be initiated.

Results

A number of open label studies, uncontrolled observations, a limited number of placebo-controlled clinical trials and valuable data from registries have demonstrated an ERT-associated reduction in neuropathic pain, gastrointestinal symptoms, slowing of renal function loss as well as slower progression of heart disease and an improvement in quality of life.

Conclusion

Whether prolongation of life of patients with this severe diasease will be achieved and whether there are differences between the two enyme preparations with respect to clinical endpoints, such as the prevention of heart failure, stroke and death through ERT has not been demonstrated in randomized controlled clinical trials yet.

Keywords

Fabry disease Enzyme replacement therapy Alpha-galactosidase A Agalsidase alfa Agalsidase beta 
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Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. C. Kurschat erhielt Vortragshonorare und Reisekosten der Firmen Genzyme und Shire. F. Grundmann erhielt Reisekosten der Firma Shire. T. Benzing gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Klinik II für Innere Medizin – Nephrologie, Rheumatologie, Diabetologie und Allgemeine Innere MedizinUniversitätsklinik KölnKölnDeutschland
  2. 2.Zentrum für Molekulare Medizin KölnUniversitätsklinik KölnKölnDeutschland

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