Trial of Cinpanemab in Early Parkinson's Disease.

BACKGROUND: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease. METHODS: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2 ratio, participants with early Parkinson's disease to receive intravenous infusions of placebo (control) or cinpanemab at a dose of 250 mg, 1250 mg, or 3500 mg every 4 weeks, followed by an active-treatment dose-blinded extension period for up to 112 weeks. The primary end points were the changes from baseline in the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score (range, 0 to 236, with higher scores indicating worse performance) at weeks 52 and 72. Secondary end points included MDS-UPDRS subscale scores and striatal binding as assessed on dopamine transporter single-photon-emission computed tomography (DaT-SPECT). RESULTS: Of the 357 enrolled participants, 100 were assigned to the control group, 55 to the 250-mg cinpanemab group, 102 to the 1250-mg group, and 100 to the 3500-mg group. The trial was stopped after the week 72 interim analysis owing to lack of efficacy. The change to week 52 in the MDS-UPDRS score was 10.8 points in the control group, 10.5 points in the 250-mg group, 11.3 points in the 1250-mg group, and 10.9 points in the 3500-mg group (adjusted mean difference vs. control, -0.3 points [95% confidence interval {CI}, -4.9 to 4.3], P = 0.90; 0.5 points [95% CI, -3.3 to 4.3], P = 0.80; and 0.1 point [95% CI, -3.8 to 4.0], P = 0.97, respectively). The adjusted mean difference at 72 weeks between participants who received cinpanemab through 72 weeks and the pooled group of those who started cinpanemab at 52 weeks was -0.9 points (95% CI, -5.6 to 3.8) for the 250-mg dose, 0.6 points (95% CI, -3.3 to 4.4) for the 1250-mg dose, and -0.8 points (95% CI, -4.6 to 3.0) for the 3500-mg dose. Results for secondary end points were similar to those for the primary end points. DaT-SPECT imaging at week 52 showed no differences between the control group and any cinpanemab group. The most common adverse events with cinpanemab were headache, nasopharyngitis, and falls. CONCLUSIONS: In participants with early Parkinson's disease, the effects of cinpanemab on clinical measures of disease progression and changes in DaT-SPECT imaging did not differ from those of placebo over a 52-week period. (Funded by Biogen; SPARK ClinicalTrials.gov number, NCT03318523.).

Spontaneous kicking in full-term and preterm infants with and without white matter disorder.

Early damage to white matter of the brain may have developmental consequences for prematurely born infants including the coordination of leg movements. Our perspective is that white matter damage initiates an ontogenetic course that may lead to movement dysfunction leading to disability. In this study, spontaneous kicking in the human infant is a "window" for evaluating the potential consequences of perinatal brain damage for sensori-motor coordination. We compare the intra-limb coordination patterns of 5-month-old premature infants with white matter damage (PTWMD) to a group of prematurely born infants without WMD (PT) and a group of full-term (FT) infants. The PT group demonstrates advanced kicking patterns in comparison to both the PTWMD and FT groups. The PTWMD group has less mature patterns than the FT group on some, but not all measures. The movement challenge for PTWMD infants may be in the transition from spontaneous kicking to movements with the legs that require decoupling of intralimb joints.

Continuous monitoring of functional activities using wearable, wireless gyroscope and accelerometer technology.

The development of functional activity monitors (FAMs) will allow rehabilitation researchers and clinicians to evaluate treatment efficacy, to monitor compliance to exercise instructions, and to provide real time feedback in the treatment of movement disorders during the performance of daily activities. The purpose of the present study was to develop and test a small sized wearable FAM system comprised of three sensors positioned on the sternum and both thighs, wireless Bluetooth transmission capability to a smartphone, and computationally efficient activity detection algorithms for the accurate detection of functional activities. Each sensor was composed of a tri-axial accelerometer and a tri-axial gyroscope. Computationally efficient activity recognition algorithms were developed, using a sliding window of 1 second, the variability of the tilt angle time series and power spectral analysis. In addition, it includes a decision tree that identifies postures such as sitting, standing and lying, walking at comfortable, slow and fast speeds, transitions between these functional activities (e.g, sit-to-stand and stand-to-sit), activity duration and step frequency. In a research lab setting the output of the FAM system, video recordings and a 3D motion analysis system were compared in 10 healthy young adults. The results show that the agreement between the FAM system and the video recordings ranged from 98.10% to 100% for all postures, transfers and walking periods. There were no significant differences in activity durations and step frequency between measurement instruments.