Gene therapy approaches for Parkinson’s disease

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Background

The field of Gene Therapy in the CNS has recently witnessed a number of major conceptual changes. Besides the traditional thinking that comprises the use of viral vectors for the delivery of a given therapeutic gene, a number of original approaches have been recently envisaged, focused on using viral vectors carrying genes to further modify brain circuits of interest. It is expected that these approaches will ultimately result in a therapeutic potential being sustained by induced changes in brain circuits. Moreover, for the first time these approaches will allow the implementation of “disease-modifying” therapies, e.g. trying to slow-down, stop or even revert the natural course of Parkinson’s disease. By taking advantage of these newly-developed techniques, it is currently feasible to (i) selectively remove any given brain circuit, (ii) to reconstruct damaged circuits as well as (iii) to generate new circuits by direct in vivo reprogramming (besides a number of few more ongoing possibilities). It is worth noting that most of these approaches have been properly validated in relevant animal models of Parkinson’s disease and are therefore quite close to clinical translation. In summary, a number of unprecedented possibilities have been made available and therefore the use of gene therapy tools for the treatment of neurodegenerative diseases cannot longer be viewed as a chimerical approach.

Moreover, a number of viral vectors have been recently envisaged and tested in an attempt to generate new animal models of Parkinson’s disease. Most of these approaches are dealing with different ways for overexpressing alpha-synuclein within dopaminergic neurons in the substantia nigra. It is expected that this new generation of animal models will soon replace most of the currently available animal models that largely stand on the use of dopaminergic neurotoxins.

The use of gene therapy tools for the treatment of Parkinson’s disease (PD) is at the center of an ongoing, heated debate. The purpose of this Research Topic is to provide potential readers with a landscape view of what’s going on in the field of gene therapy for the treatment of PD. Although PD is the main focus of this proposed symposium, the Co-Editors will encourage both solicited and unsolicited contributors speakers to prepare their manuscripts bearing in mind the multidisciplinary background of Frontiers’ expected audience. In this regard, we strongly believe that most of the provided information will be very valuable for the development of gene therapy strategies with a focus well beyond the PD field.

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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