Safety and tolerability of inebilizumab (MEDI-551), an anti-CD19 monoclonal antibody, in patients with relapsing forms of multiple sclerosis: Results from a phase 1 randomised, placebo-controlled, escalating intravenous and subcutaneous dose study.

Background: B cells may be involved in the pathophysiology of multiple sclerosis (MS). Inebilizumab (formerly MEDI-551) binds to and depletes CD19 B cells.

Objectives: To assess safety, tolerability, pharmacokinetics, pharmacodynamics and immunogenicity of inebilizumab in adults with relapsing MS.

PARK2 variability in Polish Parkinson's disease patients--interaction with mitochondrial haplogroups.

Aims And Objectives: A new pathomechanism of Parkinson's disease (PD) involving regulation of mitochondrial functions was recently proposed. Parkin complexed with mitochondrial transcription factor A (TFAM) binds mtDNA and promotes mitochondrial biogenesis, which is abolished by PARK2 gene mutations. We have previously shown that mitochondrial haplogroups/clusters and TFAM common variation influenced PD risk.

Pharmacokinetic-pharmacodynamic modeling of levodopa in patients with advanced Parkinson disease.

Objectives: The aims of the present study were to investigate the pharmacokinetic and pharmacodynamic (pk/pd) relationship of levodopa (l-dopa) in patients with advanced Parkinson disease (PD) and also to evaluate the effect of tolcapone on the pk/pd analysis of l-dopa in 1 patient with severe dyskinesias and fluctuations.

Methods: The pharmacokinetics (plasma concentrations of l-dopa and 3-O-methyldopa [3-OMD]) and motor effects (global score of the Unified Parkinson's Disease Rating Scale-III) of a single dose of l-dopa (plus the peripheral decarboxylase inhibitor 1:4) were determined in 14 patients with advanced PD. Patients were classified into 2 groups according to Hoehn and Yahr scale (stages 2 and 3).

[The role of estrogens in Parkinson's disease].

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder of the central nervous system. It has a high prevalence, which significantly increases with age. This disease significantly deteriorates the quality of life and, despite treatment, may lead to disability.

Mitochondrial transcription factor A variants and the risk of Parkinson's disease.

The mitochondrial transcription factor A (TFAM) has been recently shown to decrease reactive oxygen species (ROS) generation. It is also known that mitochondrial DNA (mtDNA) haplogroups might confer different coupling properties, resulting in different ROS levels. We hypothesized that potentially functional TFAM variants could influence PD risk depending on haplogroup background.

Association study of GATA-2 transcription factor gene (GATA2) polymorphism and Parkinson's disease.

It was shown that high levels of alpha-synuclein in substantia nigra are essential in pathogenesis of Parkinson disease (PD), and SNCA expression in neurons is controlled by GATA-2 transcription factor, which plays also crucial role in central nervous system development, and erythroid cells differentiation. Recently, significant association of two GATA2 SNPs with early-onset coronary artery disease has been presented. In this case-control study we tested a hypothesis that polymorphism of GATA2 gene may be associated with sporadic PD.

Mitochondrial DNA haplogroups and subhaplogroups are associated with Parkinson's disease risk in a Polish PD cohort.

mtDNA common variation is inconsistently reported to modify the risk of Parkinson's disease (PD). We evaluated the impact of the mitochondrial haplogroups, subhaplogroups, coding and non-coding single-nucleotide polymorphisms on PD risk in 241 PD patients and 277 control subjects. After stratification by gender, we found that haplogroup J (OR 0.

The association of functional catechol-O-methyltransferase haplotypes with risk of Parkinson's disease, levodopa treatment response, and complications.

Introduction: Differences in catechol-O-methyltransferase (COMT) activity and genotype may determine individual variations in the therapeutic response to levodopa or Parkinson's disease (PD) susceptibility. The role of functional COMT haplotypes in PD susceptibility and treatment response has not been examined.

Objectives: In this case-control study, we investigated the association of the most common COMT gene haplotypes (formed by single nucleotide polymorphisms (SNPs): rs6269:A>G; rs4633C>T; rs4818:C>G; and rs4680:A>G) with PD risk and the association of the COMT haplotypes with the dose and complications of levodopa therapy in PD patients.

[Pharmacogenetics in Parkinson's disease treatment].

The authors present the current opinion on the significance of molecular biology in individualized therapy. Pharmacogenetics is a new branch of clinical pharmacology dealing with the influence of genetic factors on drugs with special focus on interpersonal differences to drug response. The article includes basic rules of pharmacogenetics as well as its use in clinical practice.

Interleukin-10 gene polymorphism in Parkinson's disease patients.

Background: The etiology of sporadic Parkinson's disease (PD) is not well established. Recent studies revealed that inflammatory processes might also play an important role in the pathogenesis of PD. We hypothesized that genetically determined differences in the immune response, especially in anti-inflammatory cytokines production, might influence the risk of sporadic PD development and/or onset.

Corticobasal degeneration -- clinico-pathological considerations.

Corticobasal degeneration (CBD) is a rare sporadic 4-repeat tauopathy. We report here the first Polish case of pathologically proven CBD. Our patient developed clumsiness of the right hand at age 63 years.

CARD15 variants in patients with sporadic Parkinson's disease.

Recent reports have proven the importance of genetic factors and inflammation in the pathogenesis of sporadic Parkinson's disease (PD). In the current study, the frequency of CARD15/NOD2 gene variants (R702W, G908R, L1007fs), previously associated with Crohn's disease--a common inflammatory bowel disease, have been examined in a group of 308 sporadic PD patients and 220 healthy controls. Significantly higher frequency of total CARD15 variant alleles in PD patients (13.

Polymorphism in semaphorin 5A (Sema5A) gene is not a marker of Parkinson's disease risk.

A SNP rs7702187 within the semaphorin 5A gene (Sema5A) has been recently associated with sporadic Parkinson's disease (PD) risk in American Caucasians. In the present study frequencies of rs7702187 was determined in two independent populations involving 427 sporadic PD patients (235 Polish Caucasians and 192 Asians from Singapore) and 412 healthy controls (220 Caucasians and 192 Asians), with the use of PCR-RFLP assay. The frequencies of the minor allele were found to be very similar in PD patients and healthy controls in both populations studied: 0.

[The role of environmental factors in Parkinson's disease may depend on disease onset age].

Background And Purpose: Various factors are suspected to participate in PD onset and include environment-related factors and workplace exposure to pesticides, metals and hydrocarbons. Nevertheless, results of epidemiological research are inconsistent. Some authors emphasize hydrocarbons exposure to younger patients.

[Polymorphism of N-acetyltransferase-2 and pathogenesis of neoplastic diseases].

Pathogenesis of many diseases is connected with influence of environmental factors with individual genetic sensitivity dependent among others on detoxification enzymes. Mutations of N-acetyltransferase-2 lead to decreased enzyme function. In this review the focus is on discussion about the connection between the polymorphic N-acetyltransferase-2 and increase in the risk of cancer, atopic disease and adverse drug effects.

Analysis of LRRK 2 G 2019 S and I 2020 T mutations in Parkinson's disease.

Mutations in the leucine-rich repeat kinase 2 (LRRK 2), encoding dardarin protein, have been demonstrated to be linked to autosomal dominant Parkinson's disease (PD). In the present study the entire exon 41 of LRRK 2 gene was evaluated in a series of 174 PD patients recruited from Polish population, aged at the time of diagnosis 54.0+/-39.

Catechol-O-methyltransferase and monoamine oxidase B genes and susceptibility to sporadic Parkinson's disease in a Polish population.

Recent reports have proved that genetic factors play a role in the pathogenesis of sporadic Parkinson's disease (PD). It has been suggested that polymorphisms in monoamine oxidase B (MAOB) and catechol-O-methyltransferase (COMT) might increase the risk of PD. A total of 210 Polish patients with sporadic PD and 152 healthy controls were studied.

Analysis of MDR1 haplotypes in Parkinson's disease in a white population.

The MDR1 multidrug transporter is important in regulating environmental xenobiotics and hence may play a causative role in Parkinson's disease (PD). MDR1 haplotype comprising 2677 G > T/A and 3435 C > T may be protective against PD. Using a case control methodology, we investigated the association of MDR1 haplotypes (single nucleotide polymorphisms (SNPs) 2677 G > T/A and 3435 C > T) in a Polish PD population.

[The role of N-acetyltransferase polymorphism in the pathogenesis of Parkinson's disease].

Pathogenesis of many diseases is related to the influence of noxious environmental agents coupled with individual genetic sensitivity that depends on the function of detoxificating enzymes. One of the latter is N-acetyltransferase 2 whose mutations lead to an impairment of the enzyme function. Genetically determined acetylation rate reduction with exposure to neurotoxins may contribute to the development of Parkinson's disease (PD).