Nicotine Bitartrate Reduces Falls and Freezing of Gait in Parkinson Disease: A Reanalysis

Objective: Determine if NC001, an oral formulation of nicotine that reduces levodopa-induced dyskinesias (LIDs) in MPTP-Parkinson monkeys, could reduce falls, freezing of gait (FOG), and LIDs in Parkinson disease (PD) patients. Methods: Previously collected data from a study analyzing the effects of NC001 on LIDs in PD patients were reanalyzed. Because indirect-acting cholinergic drugs are sometimes helpful in reducing falls, we hypothesized that NC001, a direct-acting cholinergic agonist, could reduce falls in PD. The original 12-center, double-blind, randomized trial enrolled 65 PD patients. NC001 or placebo was administered 4 times per day for 10 weeks, beginning at 4 mg/day and escalating to 24 mg/day. Assessments included the Unified Dyskinesia Rating Scale (UDysRS) and Parts II-III of the original Unified Parkinson\u27s Disease Rating Scale (UPDRS). Results: Randomization (1:1) resulted in 35 patients on NC001 and 30 on placebo at baseline. Thirty and 27 patients, respectively, had data available for an intent-to-treat analysis. NC001 was safe and well-tolerated. After 10 weeks, NC001 patients (14/30) had a significant reduction in falls vs. placebo patients (3/27) (p = 0.0041) as assessed by UPDRS Part II. NC001 patients (12/30) also had significantly reduced FOG vs. placebo patients (4/27) (p = 0.0043). NC001 patients, compared with placebo patients, had a significant improvement (p = 0.01) in UDysRS ambulation subtest (40% vs. 3%, respectively). Although NC001 patients had a greater reduction in dyskinesias on the UDysRS than placebo patients (30% vs. 19%, respectively), this was not significant (p = 0.09). Conclusions: NC001 significantly improved two refractory symptoms of PD, falls and FOG. The reduction in falls and FOG is attributed to selective stimulation of nicotinic receptors

Nicotine Bitartrate Reduces Falls and Freezing of Gait in Parkinson Disease: A Reanalysis

Objective: Determine if NC001, an oral formulation of nicotine that reduces levodopa-induced dyskinesias (LIDs) in MPTP-Parkinson monkeys, could reduce falls, freezing of gait (FOG), and LIDs in Parkinson disease (PD) patients.Methods: Previously collected data from a study analyzing the effects of NC001 on LIDs in PD patients were reanalyzed. Because indirect-acting cholinergic drugs are sometimes helpful in reducing falls, we hypothesized that NC001, a direct-acting cholinergic agonist, could reduce falls in PD. The original 12-center, double-blind, randomized trial enrolled 65 PD patients. NC001 or placebo was administered 4 times per day for 10 weeks, beginning at 4 mg/day and escalating to 24 mg/day. Assessments included the Unified Dyskinesia Rating Scale (UDysRS) and Parts II-III of the original Unified Parkinson's Disease Rating Scale (UPDRS).Results: Randomization (1:1) resulted in 35 patients on NC001 and 30 on placebo at baseline. Thirty and 27 patients, respectively, had data available for an intent-to-treat analysis. NC001 was safe and well-tolerated. After 10 weeks, NC001 patients (14/30) had a significant reduction in falls vs. placebo patients (3/27) (p = 0.0041) as assessed by UPDRS Part II. NC001 patients (12/30) also had significantly reduced FOG vs. placebo patients (4/27) (p = 0.0043). NC001 patients, compared with placebo patients, had a significant improvement (p = 0.01) in UDysRS ambulation subtest (40% vs. 3%, respectively). Although NC001 patients had a greater reduction in dyskinesias on the UDysRS than placebo patients (30% vs. 19%, respectively), this was not significant (p = 0.09).Conclusions: NC001 significantly improved two refractory symptoms of PD, falls and FOG. The reduction in falls and FOG is attributed to selective stimulation of nicotinic receptors.Clinical Trial Registration: Conducted under IND 105, 268, serial number 0000. ClinicalTrials.gov identifier NCT00957918

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process