Study Rationale:
During the rapid eye movement (REM) phase of sleep, when we dream, our voluntary muscles are paralyzed so that we would not act out our dreams. In REM sleep behavior disorder (RBD), patients lose this ability. In more than 80 percent of the cases, RBD progresses into Parkinson’s disease (PD) or a similar disease, and, often, RBD presents many years before the appearance of motor symptoms of PD.
Hypothesis:
We hypothesize that there are genetic elements that will allow us to identify individuals who are at risk to develop RBD and later develop PD.
Study Design:
We will analyze about 40 genes that are known or suspected to be involved in Parkinson’s disease, in three groups of individuals: RBD patients, PD patients and control volunteers. By doing so, we will be able to identify genetic markers that are associated with the risk to develop RBD and with the risk to further progress to PD.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Identifying such genetic factors will potentially allow us to identify individuals who may develop PD many years — perhaps up to several decades — before the motor symptoms start. Once better treatment options are available, predictive factors will allow the initiation of treatment much earlier. It will also potentially allow better understanding of the mechanism underlying the RBD-PD axis.
Next Steps for Development:
The results from this project should be replicated in more cohorts with larger numbers of patients.
Final Outcome
Since during the preparations for the project new genes were suggested to be involved in Parkinson’s disease (PD) and REM sleep Behavior disorder (RBD), we expended the panel of genes that we studied from 40 to 51. In addition, we conducted a study of genetic markers across the entire genome (a genome-wide association study, GWAS). The analysis of the 51 genes identified numerous genetic mutations that may lead to PD and RBD or increase the risk to develop them. Furthermore, in the GWAS analysis, we identified potential new genes that may increase the risk to develop RBD and subsequently PD. The genetic data we gathered, together with follow up of the RBD patient, will allow us to identify genetic variants that are associated with conversion from RBD to PD. Such genetic variants have the potential to serve as markers to identify individuals in an earlier stage of the disease, before the motor symptoms begin.
Publications
Gan-Or Z, Girard SL, Noreau A, Leblond CS, Gagnon JF, Arnulf I, Mirarchi C, Dauvilliers Y, Desautels A, Mitterling T, Cochen De Cock V, Frauscher B, Monaca C, Hogl B, Dion PA, Postuma RB, Montplaisir JY and Rouleau GA. Parkinson’s disease genetic loci in Rapid Eye Movement Sleep Behavior Disorder. J Mol Neurosci. 2015 Jul;56(3):617-22. doi 10.1007/s12031-015-0569-7.
Gan-Or Z, Mirelman A, Postuma RB, Arnulf I, Bar-Shira A, Dauvilliers Y, Desautels A, Gagnon JF, Leblond CS, Frauscher B, Alcalay RN, Saunders-Pullman R, Bressman SB, Marder K, Monaca C, Hogl B, Orr-Urtreger A, Dion PA, Montplaisir JY, Giladi N and Rouleau GA. GBA mutations are associated with Rapid Eye Movement Sleep Behavior Disorder. Ann Clin Transl Neurol. 31 July 2015. DOI: 10.1002/acn3.228
Gan-Or Z, Mohsin N, Girard SL, Montplaisir JY, Ambalavanan A, Strong S, Mallet V, Laurent SB, Bourassa C, Boivin M, Langlois M, Arnulf I, Högl B, Frauscher B, Monaca C, Desautels A, Gagnon JF, Postuma RB, Dion PA, Dauvilliers Y, Dupre N, Alcalay RN and Rouleau GA. The role of the melanoma gene MC1R in Parkinson disease and REM sleep Behavior Disorder. Submitted.