Neue Forschungsansätze zur axonalen Schädigung und Regeneration bei peripheren Neuropathien

Zusammenfassung

Periphere Neuropathien sind häufig mit gravierenden motorischen Defiziten vergesellschaftet, die unter anderem auf eine axonale Schädigung bzw. eine inkomplette axonale Regeneration peripherer Motoneurone zurückgeführt werden können. Trotz wissenschaftlicher Fortschritte auf diesem Gebiet gibt es momentan keine medikamentöse Therapie, um gezielt eine Regeneration geschädigter Axone bei Polyneuropathien zu unterstützen. Gründe hierfür sind zum einen, dass bei Polyneuropathien unterschiedlicher Genese teilweise Pathomechanismen beteiligt sind, die aktiv eine Regeneration peripherer Axone inhibieren können. Die Charakterisierung solcher Pathomechanismen auf zellulärer und molekularer Ebene könnte daher ein Lösungsansatz darstellen, um axonale Regeneration medikamentös zu unterstützen. Ein weiteres Problem bei der Entwicklung medikamentöser Therapien im peripheren Nervensystem (PNS) besteht darin, dass axonale Regeneration im peripheren Nervensystem mit den üblichen klinischen bzw. elektrophysiologischen Messmethoden nur unzureichend erfasst werden kann. Die Weiterentwicklung von MRT-Bildgebungsmethoden könnte ein Ansatz darstellen, um axonale Regeneration seriell und non-invasiv zu messen, um so beispielsweise den Beobachtungszeitraum bei klinischen Studien zur Regeneration im PNS zu reduzieren.

Abstract

Peripheral neuropathies are frequently associated with significant motor deficits that can be attributed to axonal injury and incomplete axonal regeneration of peripheral motoneurons. Despite significant advances in our understanding of the underlying pathogenesis, there is currently no treatment available to enhance axonal regeneration in peripheral neuropathy. One explanation is that in some neuropathic conditions there are pathomechanisms acting that are able to substantially inhibit regeneration of axons with otherwise sufficient regenerative properties. The identification of the underlying cellular and molecular pathways of these processes may open up new avenues to support axonal regeneration in the peripheral nervous system (PNS). The lack of reliable and feasible outcome measures for axonal regeneration in the PNS represents another caveat that prevents the development of new therapeutic strategies. The use of novel MRI-techniques may represent a way to overcome this hurdle for example as outcome parameter for axonal regeneration in clinical trials.

Schlüsselwörter

axonale Regeneration - Neuroinflammation - Neuroimmunologie - Autoantikörper

Key words

axonal regeneration - neuroinflammation - neuroimmunology - autoantibodies

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