Gene Therapy for Parkinson's Disease
Gene Therapy for Parkinson's Disease
The aforementioned therapies are initially effective in treating many of the symptoms of PD, but none of these have shown any definite effects on disease progression – either through neuroprotection or neurorestoration. Many potentially disease-modifying agents and approaches are in preclinical development, a process that requires extensive preclinical research, typically initially using in vitro (cell culture-based) assays through to in vivo applications using 6-hydroxydopamine (6-OHDA) rat or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models. Further preclinical assessments are usually performed in (MPTP) primate animal models of PD, (reviewed in), which can include functional imaging using fluoro-deoxyglucose-PET (FDG-PET).
Currently, the most promising novel therapies rely either on the use of gene therapy or stem cells – with the potential for overlap between these approaches. The earliest stem cell therapy trials were based on the use of transplanted human fetal mesencephalic tissue, but these were associated with variable clinical outcomes and complications. More recent research has focused on the use of genetically engineered neuroblasts, producing dopaminergic neurons in vitro from embryonic stem cells or induced pluripotent stem cells, for subsequent autologous transplantation. This form of stem cell therapy, although promising, is still at an early stage of development and not ready for use in human clinical trials. By contrast, several gene therapies have undergone human clinical trials for PD. As a class, these approaches have potential theoretical advantages, including relative tissue specificity and long-term effectiveness (months to years), properties that are particularly desirable in a chronic neurodegenerative condition such as PD.
Gene Therapies for PD
The aforementioned therapies are initially effective in treating many of the symptoms of PD, but none of these have shown any definite effects on disease progression – either through neuroprotection or neurorestoration. Many potentially disease-modifying agents and approaches are in preclinical development, a process that requires extensive preclinical research, typically initially using in vitro (cell culture-based) assays through to in vivo applications using 6-hydroxydopamine (6-OHDA) rat or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models. Further preclinical assessments are usually performed in (MPTP) primate animal models of PD, (reviewed in), which can include functional imaging using fluoro-deoxyglucose-PET (FDG-PET).
Currently, the most promising novel therapies rely either on the use of gene therapy or stem cells – with the potential for overlap between these approaches. The earliest stem cell therapy trials were based on the use of transplanted human fetal mesencephalic tissue, but these were associated with variable clinical outcomes and complications. More recent research has focused on the use of genetically engineered neuroblasts, producing dopaminergic neurons in vitro from embryonic stem cells or induced pluripotent stem cells, for subsequent autologous transplantation. This form of stem cell therapy, although promising, is still at an early stage of development and not ready for use in human clinical trials. By contrast, several gene therapies have undergone human clinical trials for PD. As a class, these approaches have potential theoretical advantages, including relative tissue specificity and long-term effectiveness (months to years), properties that are particularly desirable in a chronic neurodegenerative condition such as PD.