Ansätze zur Etablierung von Präzisionsmedizin bei der Parkinson-Krankheit mit dem Schwerpunkt Genetik

Zusammenfassung

Während Parkinson mit seiner vielfältigen und sehr individuellen Kombination aus motorischen und nichtmotorischen Symptomen zunehmend genauer charakterisiert ist, nicht zuletzt durch die Untersuchung von großen Patientenkohorten mit Deep-Phenotyping-Approach, folgt die Therapie weiterhin einem einheitlichen Schema. Durch bessere Stratifikation bieten Präzisionsmedizin-Ansätze die Möglichkeit, die Behandlung und patientenzentrierte Versorgung zu verbessern. Spezifische Therapien für den Einsatz bei monogenetischen Parkinson-Formen, die aktuell untersucht werden, könnten helfen, Krankheitsmechanismen zu verstehen und dadurch auch zum Verständnis des idiopathischen Parkinson-Syndroms beitragen, sowie neue Behandlungsziele aufzeigen. Wir zeigen Daten zur Vorhersage von Wirksamkeit und Langzeit-Vorteil von aktuellen medikamentösen Behandlungen sowie von Tiefer Hirnstimulation (THS) im Kontext von wachsendem pharmakogenetischen Wissen. Konfrontiert mit asymptomatischen Trägern genetischer Mutationen (monogenetische Erkrankung) von variabler Penetranz und prodromalen Stadien wie REM-Schlaf-Verhaltensstörungen, zeichnen sich erste präventive Therapiestrategien ab. Ihr Einfluss auf die Krankheitsprogression und Aussichten für die klinische Praxis müssen adressiert werden.

Abstract

The diverse and highly individual presentations of Parkinson’s disease (PD) as a complex combination of motor and non-motor symptoms are being increasingly well characterised not least through large patient cohorts applying deep phenotyping. However, in terms of treatment of PD, the approach is uniform and purely symptomatic. Better stratification strategies with better precision medicine approaches offer opportunities to improve symptomatic treatment, define first causative therapies and provide more patient-centred care. Insight from targeted therapies for monogenic forms of PD aiming at neuroprotection may pave the way for new mechanism-based interventions also for the more common idiopathic PD. Improved stratification of patients may support symptomatic treatments by predicting treatment efficacy and long-term benefit of current pharmacological or neuromodulatory therapies, e.g. in the context of emerging pharmacogenomic knowledge. Based on asymptomatic carriers with monogenic PD or patients with REM sleep behaviour disorder (RBD), first options for applying preventive treatments emerge. The implications of these treatment strategies in relation to disease progression, and the prospects of their implementation in clinical practice need to be addressed.

Schlüsselwörter

Präzisionsmedizin - Personalisierte Medizin - Stratifizierung - Parkinson-Krankheit - Genetik

Key words

Precision Medicine - Personalised Medicine - Stratification - Parkinson’s disease - Genetics

Publication History

Received: 30 January 2020

Accepted: 28 March 2020

Article published online:
02 June 2020

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