Publications by authors named "Peter Lewitt"

Anticholinergic (AC) drugs, a medication class that acts by blocking nicotinic and muscarinic acetylcholine receptors, were first utilized for therapeutic purposes in the mid-19th century. Initial applications were as symptomatic therapy for Parkinson disease (PD), a practice continuing to the present. Initially, the AC drugs used were naturally-occurring plant compounds.

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Background: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease.

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Background: Preclinical evidence suggests that co-administration of the 5-HT agonist buspirone and the 5-HT agonist zolmitriptan act synergistically to reduce dyskinesia to a greater extent than that achieved by either drug alone.

Objectives: Assess the therapeutic potential of a fixed-dose buspirone and zolmitriptan combination in Parkinson's disease (PD) patients with levodopa-induced dyskinesia.

Methods: Single-center, randomized, placebo-controlled, two-way crossover study (NCT02439203) of a fixed-dose buspirone/zolmitriptan regimen (10/1.

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Importance: Levodopa has a short half-life and a limited window of opportunity for absorption in the proximal small intestine. IPX203 is an oral, extended-release formulation of carbidopa-levodopa developed to address these limitations.

Objective: To assess the efficacy and safety of IPX203 vs immediate-release carbidopa-levodopa in patients with Parkinson disease who are experiencing motor fluctuations.

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In the advanced Parkinson's disease, motor and non-motor symptoms become more severe and more difficult to treat. Oral therapy may become insufficient in controlling a patient´s motor complications, which results in a substantial deterioration of the patient's quality of life, ability to work and self-reliance. This is when device-aided treatments should be considered and offered, if suitable for a given patient.

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Patients with Parkinson's disease often suffer from OFF symptoms disrupting their daily routines and adding to disabilities. Despite polypharmacy and adjustments to medication schedules, they often do not experience consistent relief from their motor symptoms. As the disease progresses, impaired gastric emptying may evolve, making it even more challenging for dopaminergic drugs to provide consistent results.

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Introduction: IPX203 is a novel oral extended-release (ER) formulation of carbidopa (CD) and levodopa (LD) developed to address the short half-life and limited area for absorption of LD in the gastrointestinal tract. This paper presents the formulation strategy of IPX203 and its relationship to the pharmacokinetics (PK) and pharmacodynamic profile of IPX203 in Parkinson's disease (PD) patients.

Methods: IPX203 was developed with an innovative technology containing immediate-release (IR) granules and ER beads that provides rapid LD absorption to achieve desired plasma concentration and maintaining it within the therapeutic range for longer than can be achieved with current oral LD formulations.

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Parkinson's disease (PD) is a neurodegenerative disorder that leads to the degeneration of dopaminergic neurons resulting in a widespread pathology of motor and non-motor symptoms. Oral levodopa remains the most effective symptomatic treatment of PD, but motor complications such as Off episodes occur over time. The spectrum of manifestation of OFF episodes varies, e.

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Oral levodopa is the most effective treatment for Parkinson disease, but OFF periods emerge over time. Gastrointestinal dysfunction and food effects impact levodopa absorption, contributing to unpredictable control of OFF periods. Inhaled levodopa powder (Inbrija) is approved for on-demand treatment of OFF periods in patients receiving oral levodopa-dopa decarboxylase inhibitors.

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Objectives: Levodopa (LD) administered with dopa decarboxylase inhibitor is predominantly metabolized in the periphery by catechol- O -methyltransferase (COMT) to 3- O -methyldopa (3-OMD). Catechol- O -methyltransferase inhibition can improve treatment outcomes by decreasing variability in circulating LD concentrations. Opicapone is a once-daily COMT inhibitor approved in the US adjunctive to carbidopa (CD)/LD in patients with Parkinson disease experiencing "OFF" episodes.

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Background: Reliable and sensitive biomarkers are needed for enhancing and predicting Parkinson's disease (PD) diagnosis.

Objective: To investigate comprehensive metabolomic profiling of biochemicals in CSF and serum for determining diagnostic biomarkers of PD.

Methods: Fifty subjects, symptomatic with PD for ≥5 years, were matched to 50 healthy controls (HCs).

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Background: While treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated with the development of motor complications, that correlate to fluctuating levodopa plasma concentrations, limiting its clinical utility. Continuous infusion is considered to be the optimal delivery route for treating PD patients with motor fluctuations, but current infusion systems require invasive surgery. Subcutaneous infusion of (SC) levodopa has the potential to provide a better tolerated and more convenient route of continuous levodopa delivery.

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MRI has been used to develop biomarkers for movement disorders such as Parkinson disease (PD) and other neurodegenerative disorders with parkinsonism such as progressive supranuclear palsy and multiple system atrophy. One of these imaging biomarkers is neuromelanin (NM), whose integrity can be assessed from its contrast and volume. NM is found mainly in certain brain stem structures, namely, the substantia nigra pars compacta (SNpc), the ventral tegmental area, and the locus coeruleus.

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Background: There is limited information on optimization of symptomatic management of cervical dystonia (CD) after implantation of pallidal deep brain stimulation (DBS).

Objectives: To describe the long-term, "real-world" management of CD patients after DBS implantation and the role of reintroduction of pharmacologic and botulinum toxin (BoNT) therapy.

Methods: A retrospective analysis of patients with focal cervical or segmental craniocervical dystonia implanted with DBS was conducted.

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Mutations in leucine-rich repeat kinase 2 () are the most common genetic risk factors for Parkinson's disease (PD). Increased LRRK2 kinase activity is thought to impair lysosomal function and may contribute to the pathogenesis of PD. Thus, inhibition of LRRK2 is a potential disease-modifying therapeutic strategy for PD.

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Article Synopsis
  • The study aimed to evaluate whether increasing urate levels through inosine treatment can slow down the progression of early Parkinson's disease, using data that suggests urate elevation might be beneficial.* -
  • Conducted as a phase 3 trial, 298 participants with early-stage Parkinson's disease were randomly assigned to receive either inosine to elevate serum urate levels or a placebo, over a period of up to 2 years.* -
  • Results from the study indicated no significant differences in clinical progression rates between the inosine and placebo groups, leading to an early closure of the trial based on an interim analysis.*
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Background: Continuous, subcutaneous (SC) levodopa/carbidopa infusion with ND0612 is under development as a treatment for patients with Parkinson's disease (PD) and motor fluctuations.

Objective: Evaluate 1-year safety data.

Methods: BeyoND is an open-label study evaluating the long-term safety of two ND0612 dosing regimens.

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Background: Istradefylline is a selective adenosine A2A receptor antagonist for the treatment of patients with Parkinson's disease (PD) experiencing OFF episodes while on levodopa/decarboxylase inhibitor.

Objective: This pooled analysis of eight randomized, placebo-controlled, double-blind phase 2b/3 studies evaluated the efficacy and safety of istradefylline.

Methods: Istradefylline was evaluated in PD patients receiving levodopa with carbidopa/benserazide and experiencing motor fluctuations.

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