Gene therapy approaches to enhance regeneration of the injured peripheral nerve.

Peripheral nerve injury in humans often leads to incomplete functional recovery. In this review we discuss the potential for gene therapy to be used as a strategy alongside surgical repair techniques for the study of peripheral nerve regeneration in rodent models and with a view to its eventual use for the promotion of successful regeneration in the clinic. Gene therapy can be defined as the introduction of a foreign, therapeutic gene into living cells in order to treat a disease. The first attempts to express a foreign gene in peripheral neurons date back more than 25 years. The vectors used at that time were imperfect-mainly because they contained viral genes that were expressed in the target cells and elicited an immunological response. Fortunately significant progress has been made: today adeno-associated viral vectors can be produced completely free of viral genes and Phase I and II clinical studies have shown that these vectors are well tolerated. The technology for gene delivery has reached a state of readiness for clinical translation in many fields of neurology, including peripheral nerve repair. The current range of potential therapeutic genes for the repair of the traumatized peripheral nerve has also grown over the years and now includes neurotrophic factors with specificities for various subtypes of peripheral neurons, cell adhesion and extracellular matrix molecules and transcription factors. This review for this Festschrift, published to celebrate the 70th birthday of Willem Hendrik Gispen, contains many "footprints" from the time the senior author (JV) worked with Willem Hendrik, first as a student intern, then as a Ph.D. student (1983-1987) and later as a postdoctoral fellow (1989-1993). The preface of this article highlights personal memories of a time that will never come back.