Trial of Cinpanemab in Early Parkinson’s Disease Lang, Anthony E.; Siderowf, Andrew D.; Macklin, Eric A. ...
New England journal of medicine/The New England journal of medicine,
08/2022, Letnik:
387, Številka:
5
Journal Article
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In a phase 2 trial in early Parkinson’s disease, treatment with cinpanemab, a monoclonal antibody to α-synuclein, did not affect clinical or imaging progression over a period of 72 weeks.
Clinical rating scales typically includes subjective evaluations, and their time-limited duration may fail to capture daily fluctuations in motor symptoms resulting from Parkinson's disease (PD). ...Recently, a new tool (i.e. the PD-Watch) has been proposed for the objective and continuous assessment of PD motor manifestations based on evaluating frequency data from a wrist-worn tri-axial accelerometer and identifying specific movement patterns typically associated with disorders. This reduces the probability of confusing physiological or pathological movements occurring at the same frequency. In this work, we present a new method for assessing motor fluctuations through a wrist-worn accelerometer. We also explore the agreement between the continuous data generated by the proposed method and data reported in the patient diaries. In this study, twelve PD patients were recruited with an overall recording duration of 528 hours. Results of this preliminary study show that the proposed tool has suitable and adequate performances for analysing the motor signs of PD patients, and the estimated sensitivity, specificity, and accuracy of the tool are 85%, 94%, and 91%, respectively.
Levodopa-induced motor complications are a common source of disability for patients with Parkinson's disease. Evidence suggests that motor complications are associated with non-physiological, ...pulsatile stimulation of dopamine receptors. In healthy brains, dopamine neurons fire continuously, striatal dopamine concentrations are relatively constant, and there is continuous activation of dopamine receptors. In the dopamine-depleted state, standard levodopa therapy does not normalise the basal ganglia. Rather, levodopa or other short-acting dopaminergic drugs induce molecular changes and altered neuronal firing patterns in basal ganglia neurons leading to motor complications. The concept of continuous dopaminergic stimulation proposes that continuous delivery of a dopaminergic drug will prevent pulsatile stimulation and avoid motor complications. In monkeys treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and patients with Parkinson's disease, long-acting or continuous infusion of a dopaminergic drug reduces the risk of motor complications. The current challenge is to develop a long-acting oral formulation of levodopa that provides clinical benefits but avoids motor complications.
Levodopa is the most efficacious treatment in the management of Parkinson's disease. Unfortunately, chronic use of traditional levodopa/dopa decarboxylase inhibitor formulations is associated with ...the development of complications, such as wearing-off and dyskinesia. In an attempt to avoid these complications, some physicians delay the introduction of levodopa or employ levodopa-sparing strategies; however, these strategies are frequently suboptimal for patients. As most patients require the superior efficacy of levodopa during the course of their disease, an appreciation of the changing response to levodopa over time and an understanding of the pharmacokinetic principles underlying the development of complications such as wearing-off is essential in the long-term management of the patient.
Chronic constipation is a highly prevalent and often under-appreciated gastrointestinal disorder in PD associated with significant impairment in quality of life. In this study, we investigated the ...efficacy and safety of PHGG plus hyaluronate (PHGG+) in patients suffering from PD and constipation. Thirty-four PD patients have been recruited in an open-label pilot study and measured symptoms and quality of life instruments related to constipation. PHGG+ showed to have a minimal still significant effect in improving constipation as measured by PAC Symp and CGI-S. PHGG+ is safe and well tolerated. Data suggests that PHGG+ may be considered efficacious in alleviating symptoms of constipation in PD patients. Trial registration number: NCT04569656/24 Sept. 2020