TITLE:
Gene therapy for Parkinson’s Disease and Ethical Challenges: A Systematic Review
AUTHORS:
Théodora M. Zohoncon, Joseph Sawadogo, Abdou Azaque Zoure, Abdoul Karim Ouattara, Marie N. L. Ouedraogo, Luc Zongo, Paul Ouedraogo, Florencia W. Djigma, Christelle W. M. Nadembèga, Raphael Kabore, Djénéba Ouermi, Dorcas Obiri-Yeboah, Jacques Simpore
KEYWORDS:
Neurodegenerative Diseases, Parkinson Disease, Molecular Mechanism, Gene Therapy, Gene Therapy Ethics
JOURNAL NAME:
Advances in Parkinson's Disease,
Vol.12 No.2,
May
31,
2023
ABSTRACT: Background: Parkinson’s disease (PD) is a complex, multifactorial neurodegenerative disorder with a pathophysiology deriving from the synergy of abnormal aggregation of neuroinflammation, synuclein and dysfunction of lysosomes, mitochondria and synaptic transport difficulties influenced by genetic and idiopathic factors. Worldwide, PD has a prevalence of 2-3% in people over the age of 65. To date, there is no certified, effective treatment for PD. Aim: The aims of this research were: (i) to present, on the basis of recent advances in molecular genetics and epigenetics, the genomic aspects and challenges of gene therapy trials for PD; (ii) to outline the ethical principles applicable to therapeutic trials for PD. Method: A systematic literature review was carried out to identify relevant articles reporting on genomic aspects and gene therapy in PD from 2001 to October 2023. The search was conducted in French and/or English in three databases: PubMed, Google Scholar and Science Direct. PRISMA guidelines were used in this systematic review. Results: A total of thirty-three publications were selected. An inductive thematic analysis revealed that numerous genetic mutations (SNCA, Parkin, PINK1, DJ-1, LRRK2, ATP13A2, VPS35, Parkin/PRKN, PINK1, DJ1/PARK7) and epigenetic events such as the action of certain miRNAs (miR-7, miR-153, miR-133b, miR-124, miR-137) are responsible for the onset of PD, and that genetic therapy for this pathology raises ethical questions that need to be elucidated in the light of the bioethical principles of autonomy, beneficence, non-maleficence and justice. Conclusion: There is no zero risk in biotechnology. Then, it will be necessary to assess all the potential risks of Parkinson disease’s gene therapy to make the right decision. It is therefore essential to pursue research and, with the guidance of ethics, to advance treatment options and meet the challenges of brain manipulation and its impact on human identity. The golden rule of medicine remains: “Primum non nocere”.