Clinical phase I/II studies have demonstrated the safety of gene therapy for a variety of central nervous system disorders, including Canavan's, Parkinson's (PD) and Alzheimer's disease (AD),... Show moreClinical phase I/II studies have demonstrated the safety of gene therapy for a variety of central nervous system disorders, including Canavan's, Parkinson's (PD) and Alzheimer's disease (AD), retinal diseases and pain. The majority of gene therapy studies in the CNS have used adeno-associated viral vectors (MV) and the first AAV-based therapeutic, a vector encoding lipoprotein lipase, is now marketed in Europe under the name Glybera. These remarkable advances may become relevant to translational research on gene therapy to promote peripheral nervous system (PNS) repair. This short review first summarizes the results of gene therapy in animal models for peripheral nerve repair. Secondly, we identify key areas of future research in the domain of PNS-gene therapy. Finally, a perspective is provided on the path to clinical translation of PNS-gene therapy for traumatic nerve injuries. In the latter section we discuss the route and mode of delivery of the vector to human patients, the efficacy and safety of the vector, and the choice of the patient population for a first possible proof-of-concept clinical study. Show less
Hoyng, S.A.; Winter, F. de; Gnavi, S.; Boer, R. de; Boon, L.I.; Korvers, L.M.; ... ; Verhaagen, J. 2014
The primary goal in repairing a peripheral nerve lesion is to guide the outgrowing axon back to its original target organ, which can be done by bridging the defect with an autograft or, more... Show moreThe primary goal in repairing a peripheral nerve lesion is to guide the outgrowing axon back to its original target organ, which can be done by bridging the defect with an autograft or, more experimentally, a synthetic nerve graft. In this thesis an overview is presented of the evaluation methods that are currently used to assess peripheral nerve regeneration and their expediency is discussed. An in vitro electrophysiological evaluation method that charts the electrophysiological properties of the myelinated Aα- and Aβ-nerve fibres was introduced, and it was demonstrated that small differences between grafted nerves could be discriminated. Moreover, the electrophysiological data could be correlated to the morphometrical data, that was likewise broken up into Aα- and Aβ-components. This correlation especially provided new insight in the changes that occur in regenerating nerve fibres. After applying a panel of evaluation methods it was demonstrated that the presence of pores in and biodegradability of synthetic nerve grafts are beneficial to regeneration, evidenced mainly by preferable values of the electrophysiological parameters. Finally the changes that occurred in reinnervated muscles helped to gain insight into the preferential architecture of a synthetic nerve graft. Show less
