Discordant Monozygotic Parkinson Disease Twins: Role of Mitochondrial Integrity

Marija Dulovic‐Mahlow I. R. König,  J. Trinh,  S. Haissatou Diaw,  P. P. Urban,  E. Knappe,  N. Kuhnke,  Lena‐Christin Ingwersen,  F. Hinrichs  J. Weber,  P. Kupnicka,  A. Balck,  S. Delcambre,  T. Vollbrandt,  A. Grünewald,  C. Klein,  P. Seibler, K. Lohmann

Annals of Neurology. First published: 23 October 2020 

Selezionato dal Lettore: Davide Norata - medico in formazione specialistica presso la Clinica Neurologica di Ancona – Università Politecnica delle Marche

Motivation: Parkinson’s disease (PD) is widely accepted as a multifactorial disease, i.e. with genetic and environmental contributions. Even when monogenic, PD phenotype has low penetrance. Despite their identical genetic and similar environmental background, monozygotic twins with PD share a concordance rate of only 20%. The reason of such variability is poorly understood. This study hypothesizes as possible answer the pathogenic role of mitochondrial dysfunctions, already previously described in idiopathic PD, in terms of different degree of inherited mitochondrial DNA heteroplasmy. Using mitochondrial integrity markers and mtDNA sequencing techniques on skin fibroblast cultures derived from PD monozygotic twins, the authors first demonstrates that molecular changes in mitochondrial integrity and somatic mtDNA variants reflect the clinical status and might act as biomarkers of disease presentation. These findings suggest that mtDNA assay might predict the individuals at higher risk to develop the disease and pave the avenue to new therapeutic strategies.