Parkinson disease therapy: current strategies and future research priorities.

Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management.

Effectiveness of an herbaceous derivatives, PHGG, plus sodium hyaluronate in the treatment of chronic constipation in patients with Parkinson's disease: a pilot study.

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.

Immunization therapies for Parkinson's disease: state of the art and considerations for future clinical trials.

Introduction: Advances in the understanding of the mechanisms that lead to Lewy body pathology in Parkinson's disease (PD) have yielded rationales for tackling neurodegeneration associated with α-Synuclein (α-Syn) misfolding, aggregation, and/or its related spreading. Immunization therapies targeting distinct α-Syn epitopes (conformational and linear) that aim to limit extracellular spread in the brain are now in development. Completed and ongoing studies have enrolled early PD patients without considering individual clinical differences and assume a common pathogenetic mechanism of the disease.

Clinical and pharmacokinetics equivalence of multiple doses of levodopa benserazide generic formulation vs the originator (Madopar).

Aims: While several generic preparations of levodopa/carbidopa and levodopa/benserazide (LBD) are currently available, pharmacokinetic (PK) equivalence and therapeutic equivalence studies with levodopa generics are not available in Italy. Lack of data on generic formulations is a critical factor for their limited use in this country and often lead patients to refuse the generic version of the branded drug.

Methods: An experimental, 2-centre, randomized, double-blind, 2-sequence, noninferiority cross-over study was designed to evaluate both the PK equivalence and clinical equivalence of multiple doses of the generic preparation of LDB, Teva Italia, compared to the originator (Madopar).

Are All Dopamine Agonists Essentially the Same?

Dopamine agonists (DAs) represent an excellent treatment option for patients with Parkinson's disease, in both the early and advanced stages of the disease, improving motor symptoms, lowering the incidence of motor complications, and addressing several non-motor symptoms. Indeed, each of these compounds have different pharmacokinetic and pharmacodynamic properties, resulting in a unique efficacy and safety profile. Comorbidities, prominent non-motor symptoms and individual subjects' clinical characteristics should guide the choice of a specific DA, allowing better management of the patient by optimizing the DA benefit/risk ratio.

Disease progression in Parkinson subtypes: the PPMI dataset.

Introduction: Discrete patterns of progression have been suggested for patients with Parkinson disease and presenting tremor dominant (TD) or postural instability gait disorders (PIGD). However, longitudinal prospective assessments need to take into consideration the variability in clinical manifestations and the evidence that only 40% of initially classified PIGD remain in this subtype at subsequent visits.

Methods: We analyzed clinical progression of PIGD compared to TD using longitudinal clinical data from the PPMI.

Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole.

Rationale: A pivotal role for glutamate in the pathophysiology and treatment of schizophrenia has been suggested. Few reports have investigated the impact of antipsychotics on postsynaptic density (PSD) molecules involved in glutamatergic transmission and synaptic remodeling. Homer is a key PSD molecule putatively implicated in schizophrenia.

Cerebral D2 and 5-HT2 receptor occupancy in Schizophrenic patients treated with olanzapine or clozapine.

We report the results of a double-blind, randomized prospective trial on D2 and 5-HT2 receptor occupancy and the clinical effects of olanzapine versus clozapine in a sample of neuroleptic-refractory schizophrenic patients. Receptor occupancy was evaluated in different cortical areas and in basal ganglia using [18F] fluoro-ethyl-spiperone ([18F] FESP) and positron emission tomography (PET). A total of 15 neuroleptic-free patients completed the study undergoing a baseline and a post-treatment PET scan (olanzapine, nine patients, one female; clozapine, six patients, three female) 8 weeks after starting treatment.

Acute administration of antipsychotics modulates Homer striatal gene expression differentially.

Typical and atypical antipsychotics, the mainstay of schizophrenia pharmacotherapy, have been demonstrated to affect differently neuronal gene expression in several preclinical paradigms. Here we report the differential gene expression of the glutamatergic post-synaptic density proteins Homer and PSD-95 in rat forebrain following acute haloperidol or olanzapine treatment. Moreover, considering the extensive interactions between dopaminergic and opioidergic systems we also measured striatal preproenkephalin mRNA.

Pergolide protects SH-SY5Y cells against neurodegeneration induced by H(2)O(2).

We found that pergolide, a dopamine D1/D2 receptor agonist used in the clinical therapy of Parkinson's disease, protects SH-SY5Y neuroblastoma cells from cell death induced by a brief pulse (15 min) of 1 mM H(2)O(2). Neuroprotection was found when pergolide was added to the culture medium either simultaneously with (EC(50)=60 nM) or 2 h before (EC(50)=40 nM) H(2)O(2) treatment. These effects were not blocked by different dopamine receptor antagonists.