Targeting kinases in Parkinson's disease: A mechanism shared by LRRK2, neurotrophins, exenatide, urate, nilotinib and lithium.

Several kinases have been implicated in the pathogenesis of Parkinson's disease (PD), most notably leucine-rich repeat kinase 2 (LRRK2), as LRRK2 mutations are the most common genetic cause of a late-onset parkinsonism that is clinically indistinguishable from sporadic PD. More recently, several other kinases have emerged as promising disease-modifying targets in PD based on both preclinical studies and clinical reports on exenatide, the urate precursor inosine, nilotinib and lithium use in PD patients. These kinases include protein kinase B (Akt), glycogen synthase kinases-3β and -3α (GSK-3β and GSK-3α), c-Abelson kinase (c-Abl) and cyclin-dependent kinase 5 (cdk5).

Characterization of Endocannabinoid-Metabolizing Enzymes in Human Peripheral Blood Mononuclear Cells under Inflammatory Conditions.

Endocannabinoid-metabolizing enzymes are downregulated in response to lipopolysaccharide (LPS)-induced inflammation in mice, which may serve as a negative feedback mechanism to increase endocannabinoid levels and reduce inflammation. Increased plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) and decreased fatty acid amide hydrolase (FAAH) activity in peripheral lymphocytes from individuals diagnosed with Huntington's disease (HD) suggests that a similar negative feedback system between inflammation and the endocannabinoid system operates in humans. We investigated whether CpG- (unmethylated bacterial DNA) and LPS-induced IL-6 levels in peripheral blood mononuclear cells (PBMCs) from non-HD and HD individuals modulated the activities of endocannabinoid hydrolases monoacylglycerol lipase (MAGL) and carboxylesterase (CES).

Telehealth Management of Parkinson's Disease Using Wearable Sensors: An Exploratory Study.

Background: Parkinson's disease (PD) motor symptoms can fluctuate and may not be accurately reflected during a clinical evaluation. In addition, access to movement disorder specialists is limited for many with PD. The objective was to assess the impact of motion sensor-based telehealth diagnostics on PD clinical care and management.

Virtual visits for Parkinson disease: A multicenter noncontrolled cohort.

Background: Previous small-scale studies have demonstrated the feasibility of providing remote specialty care via virtual visits. We assessed the feasibility and benefits of a one-time consultation between a remote Parkinson Disease (PD) specialist and an individual with PD at home on a larger scale.

Methods: We conducted a multicenter noncontrolled cohort of virtual visits administered over videoconferencing between remote PD specialists and individuals with PD in their home.

Analysis of Participant Withdrawal in Huntington Disease Clinical Trials.

Background: Excellent retention in Huntington disease (HD) clinical trials is essential for testing new therapies. The stage of disease, cognitive status, and availability of a care partner may influence retention in HD clinical trials.

Objective: We sought to analyze reasons for early withdrawal in three HD clinical trials, and evaluated if either baseline characteristics or follow-up assessments were associated with time to withdrawal.

Wearable Sensors in Huntington Disease: A Pilot Study.

Background: The Unified Huntington's Disease Rating Scale (UHDRS) is the principal means of assessing motor impairment in Huntington disease but is subjective and generally limited to in-clinic assessments.

Objective: To evaluate the feasibility and ability of wearable sensors to measure motor impairment in individuals with Huntington disease in the clinic and at home.

Methods: Participants with Huntington disease and controls were asked to wear five accelerometer-based sensors attached to the chest and each limb for standardized, in-clinic assessments and for one day at home.