A Review on Response to Device-Aided Therapies Used in Monogenic Parkinsonism and GBA Variants Carriers: A Need for Guidelines and Comparative Studies

Abstract

Parkinson’s disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring.

Precision Medicine in Parkinson’s Disease: From Genetic Risk Signals to Personalized Therapy

“…Current evidence is even more limited for other device-aided therapies (CASI and Levodopa-Carbidopa Intestinal Gel (LCIG)) in SCNA-related PD [ 283 ], but higher frequency and earlier development of dementia, hallucinations, psychosis, and autonomic dysfunction could make these approaches unsuitable as well.…”

“…Based on these findings, STN-DBS could be beneficial for motor fluctuations in SCNA-PD, despite a higher long-term risk of axial motor decline and non-motor (cognitive and psychiatric) progression [ 273 , 283 ]. Similarly, other non-surgical device-aided therapies, such as CASI, could exacerbate non-motor complications of dopaminergic stimulation.…”

“…Similarly, other non-surgical device-aided therapies, such as CASI, could exacerbate non-motor complications of dopaminergic stimulation. In these patients, LCIG seems a potentially more suitable and safe therapeutic option [ 283 ].…”

The Landscape of Monogenic Parkinson’s Disease in Populations of Non-European Ancestry: A Narrative Review

“…The genetic diagnosis of the disease is important in these cases not only for family planning and assessment of patient prognosis but also because it can be taken into account for specific therapeutic options, namely device-aided treatments [like Deep Brain Stimulation (DBS) or Levodopa-Carbidopa enteric gel pumps] and even more so for inclusion in emerging clinical studies that are applied to specific genetic forms of the disease, in the context of pharmacogenomics [2]. In the era of individualized therapies, the strategy of treatment in genetic PD forms may differ substantially compared to idiopathic PD [3].…”