Among people with young-onset Parkinson’s disease (PD), a new study finds that those who underwent deep brain stimulation (DBS) surgery were more likely to have a PD-linked genetic mutation than those who did not get DBS. The research represents a step forward in understanding how genetic mutations impact the symptoms and progression of PD, and, in turn, the benefits of DBS. The results appear in the September/October issue of Movement Disorders Clinical Practice.
Most people with young onset PD do not carry any identifiable genetic mutations, yet about 15 percent of people with PD have a relative with the disease, suggesting an underlying genetic influence. But according to a recent study, among people with PD who underwent the surgical therapy DBS, nearly twice that number — 29 percent — had a mutation in one of three PD-linked genes. In addition, DBS is increasingly being used earlier in the course of PD. These observations led scientists to ask whether younger people receiving DBS for PD also were likely to have PD genetic mutations.
For the new study, which was supported in part by the Parkinson’s Disease Foundation (PDF), scientists led by Gian D. Pal, M.D., M.S., at the PDF Research Center at Rush University Medical Center in Chicago, analyzed DNA from 793 people whose PD was diagnosed at age 50 or younger, and who had participated in an earlier study called the Consortium on Risk for Early Onset Parkinson’s Disease (CORE-PD, funded primarily by NIH, with PDF support). They also looked at demographic data and study participants’ PD symptoms as evaluated by standard tests.
- Of the 793 study participants, 99 received DBS and 684 had not.
- Among study participants receiving DBS, 26.5 percent had a mutation in one of three PD-linked genes: glucocerebrosidase (GBA), LRRK2 (leucine-rich repeat kinase 2) or parkin (PRKN), while those without DBS, only 16.8 percent had one of these mutations.
- GBA mutations were the most common mutations in both groups.
- Study participants with dyskinesia (involuntary movements that can develop after years of dopamine therapy) were more likely to be receiving DBS.
What Does It Mean?
The new research shows that people with early onset PD who are receiving DBS have more PD-linked genetic mutations than those without DBS. In particular, they were more likely to have a mutation in the GBA gene. This is not surprising, because GBA mutations are the most common risk factor for PD.
The next step will be to study how PD-linked genetic mutations affect the success of DBS. This is especially important because of the increasing emphasis on earlier DBS placement which is likely to capture more people with genetic forms of PD.
Researchers are gaining a better understanding of how mutations influence PD symptoms and progression. For example, recent studies have suggested that GBA mutations underlie faster disease progression as well as cognitive changes. It remains unknown if people with these mutations may benefit from DBS placement sooner than non-carriers, or if DBS is placed in one brain region versus another. Ultimately, the goal is to be able to select candidates for DBS who have the best chance for success, identify those with a high risk of long-term decline, and to initiate therapy at a time when it can have a lasting effect.
Pal GD, Hall D, Ouyang B, et al. (2016). Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson’s Disease. Movement Disorders doi:10.1002/mdc3.12309