Scientific rationale for the development of gene therapy strategies for Parkinson's disease

Tomas Björklund , Deniz Kirik

The ever-evolving understanding of the neuronal systems involved in Parkinson's disease together with the recent advances in recombinant viral vector technology has lead to the development of several gene therapy applications that are now entering into clinical testing phase. To date, four fundamentally different approaches have been pursued utilizing recombinant adeno-associated virus and lentiviruses as vectors for delivery. These strategies aim either to restore the lost brain functions by substitution of enzymes critical for synthesis of neurotransmitters or neurotrophic factors as a means to boost the function of remaining neurons in the diseased brain. In this review we discuss the differences in mechanism of action and describe the scientific rationale behind the currently tested gene therapy approaches for Parkinson's disease in some detail and pinpoint their individual unique strengths and weaknesses

Mots clés: neurotrophic factors; neurorestoration; neuroprotection; enzyme replacement; dopamine; tyrosine hydroxylas; 6-OHDA; AADC; COMT; DBS; DA; DAT; EIAV; FDG; FMT; GABA; GDNF; GFR; GP; GPi; Glu; GAD; GFP; GCH1; ICV; IgSP; L-DOPA; MPTP; NGF; NTN; PD; PDCP; PDRP; PPRS; PET; rAAV; rAd; rLV; BH4; 5HT; STN; SNr; TH; UPDRS; VG; viral vectors; in vivo gene transfer

Tomas Björklund, Deniz Kirik. Scientific rationale for the development of gene therapy strategies for Parkinson's disease. Biochimica et Biophysica Acta - Molecular Basis of Disease, 2009, 1792 (7), pp.703. ⟨10.1016/j.bbadis.2009.02.009⟩. ⟨hal-00492066⟩