TY - JOUR

T1 - Gene therapy for Parkinson's disease, an update

AU - Axelsen, Tobias M.

AU - Woldbye, David P.D.

PY - 2018

Y1 - 2018

N2 - The current mainstay treatment of Parkinson's disease (PD) consists of dopamine replacement therapy which, in addition to causing several side effects, does not delay disease progression. The field of gene therapy offers a potential means to improve current therapy. The present review gives an update of the present status of gene therapy for PD. Both non-disease and disease modifying transgenes have been tested for PD gene therapy in animal and human studies. Non-disease modifying treatments targeting dopamine or GABA synthesis have been successful and promising at improving PD symptomatology in randomized clinical studies, but substantial testing remains before these can be implemented in the standard clinical treatment repertoire. As for disease modifying targets that theoretically offer the possibility of slowing the progression of disease, several neurotrophic factors show encouraging results in preclinical models (e.g., neurturin, GDNF, BDNF, CDNF, VEGF-A). However, so far, clinical trials have only tested neurturin, and, unfortunately, no trial has been able to meet its primary endpoint. Future clinical trials with neurotrophic factors clearly deserve to be conducted, considering the still enticing goal of actually slowing the disease process of PD. As alternative types of gene therapy, opto- A nd chemogenetics might also find future use in PD treatment and novel genome-editing technology could also potentially be applied as individualized gene therapy for genetic types of PD.

AB - The current mainstay treatment of Parkinson's disease (PD) consists of dopamine replacement therapy which, in addition to causing several side effects, does not delay disease progression. The field of gene therapy offers a potential means to improve current therapy. The present review gives an update of the present status of gene therapy for PD. Both non-disease and disease modifying transgenes have been tested for PD gene therapy in animal and human studies. Non-disease modifying treatments targeting dopamine or GABA synthesis have been successful and promising at improving PD symptomatology in randomized clinical studies, but substantial testing remains before these can be implemented in the standard clinical treatment repertoire. As for disease modifying targets that theoretically offer the possibility of slowing the progression of disease, several neurotrophic factors show encouraging results in preclinical models (e.g., neurturin, GDNF, BDNF, CDNF, VEGF-A). However, so far, clinical trials have only tested neurturin, and, unfortunately, no trial has been able to meet its primary endpoint. Future clinical trials with neurotrophic factors clearly deserve to be conducted, considering the still enticing goal of actually slowing the disease process of PD. As alternative types of gene therapy, opto- A nd chemogenetics might also find future use in PD treatment and novel genome-editing technology could also potentially be applied as individualized gene therapy for genetic types of PD.

KW - BDNF

KW - CDNF

KW - chemogenetics

KW - dopamine

KW - GAD

KW - GDNF

KW - Gene therapy

KW - genome editing

KW - MANF

KW - neurotrophic factors

KW - NRTN

KW - optogenetics

KW - Parkinson's disease targets

U2 - 10.3233/JPD-181331

DO - 10.3233/JPD-181331

M3 - Review

C2 - 29710735

AN - SCOPUS:85048606803

VL - 8

SP - 195

EP - 215

JO - Journal of Parkinson's Disease

JF - Journal of Parkinson's Disease

SN - 1877-7171

IS - 2

ER -