Parthenolide supports PNS repair – Parthenolide and its derivatives for use in the treatment of axonal damage

In general, injured peripheral nervous tissue possesses the capacity to regenerate severed axons and therefore the ability for repair. Mechanisms of so-called neuroregeneration may include generation of new glia, extension of axons, re-myelination or restoration of functional synapses. However, the ability for neuroregeneration differs strongly between the peripheral nervous system (PNS) and the central nervous system (CNS). However, although injured axons of the peripheral nervous system show generally greater potential for intrinsic axonal regrowth, functional regeneration is often limited, mainly due to a decline in neurotrophic support from Schwann cells over time and axonal misguidance.
These aspects become particularly evident in cases of long distance regeneration, for example after sciatic nerve injury in legs or median nerve damage in arms. Therefore, the development of novel therapeutic measures aiming to accelerate axon regenera-tion and thereby improving functional recovery is highly desirable. It was found by the inventors of the present invention that the natural product parthenolide and its derivatives facilitate the axonal growth and guidance of injured peripheral nerves in cell culture and most significantly also in vivo. The inventors demonstrate that the intraneural injection of parthenolide at the regenerating nerve results in an improved functional motor recovery as well as in an improved sensory functional recovery.

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