Patients accept therapy using embryonic stem cells for Parkinson’s disease:a discrete choice experiment

Background: New disease-modifying ways to treat Parkinson’s disease (PD) may soon become a reality with intracerebral transplantation of cell products produced from human embryonic stem cells (hESCs). The aim of this study was to assess what factors influence preferences of patients with PD regarding stem-cell based therapies to treat PD in the future. Methods: Patients with PD were invited to complete a web-based discrete choice experiment to assess the importance of the following attributes: (i) type of treatment, (ii) aim of treatment, (iii) available knowledge of the different types of treatments, (iv) effect on symptoms, and (v) risk for severe side effects. Latent class conditional logistic regression models were used to determine preference estimates and heterogeneity in respondents’ preferences. Results: A substantial difference in respondents’ preferences was observed in three latent preference patterns (classes). “Effect on symptoms” was the most important attribute in class 1, closely followed by “type of treatment,” with medications as preferred to other treatment alternatives. Effect on symptoms was also the most important attribute in class 2, with treatment with hESCs preferred over other treatment alternatives. Likewise for class 3, that mainly focused on “type of treatment” in the decision-making. Respondents’ class membership was influenced by their experience in treatment, side effects, and advanced treatment therapy as well as religious beliefs. Conclusions: Most of the respondents would accept a treatment with products emanating from hESCs, regardless of views on the moral status of embryos. Preferences of patients with PD may provide guidance in clinical decision-making regarding treatments deriving from stem cells.</p

Validity and Responsiveness of At-Home Touch Screen Assessments in Advanced Parkinson's Disease

The aim of this study was to investigate if a telemetry test battery can be used to measure effects of Parkinson's disease (PD) treatment intervention and disease progression in patients with fluctuations. Sixty-five patients diagnosed with advanced PD were recruited in an open longitudinal 36-month study; 35 treated with levodopa-carbidopa intestinal gel (LCIG) and 30 were candidates for switching from oral PD treatment to LCIG. They utilized a test battery, consisting of self-assessments of symptoms and fine motor tests (tapping and spiral drawings), four times per day in their homes during week-long test periods. The repeated measurements were summarized into an overall test score (OTS) to represent the global condition of the patient during a test period. Clinical assessments included ratings on unified PD rating scale (UPDRS) and 39-item PD questionnaire (PDQ-39) scales. In LCIG-naive patients, the mean OTS compared to baseline was significantly improved from the first test period on LCIG treatment until month 24. In LCIG-non naive patients, there were no significant changes in the mean OTS until month 36. The OTS correlated adequately with total UPDRS (rho = 0.59) and total PDQ-39 (0.59). Responsiveness measured as effect size was 0.696 and 0.536 for OTS and UPDRS, respectively. The trends of the test scores were similar to the trends of clinical rating scores but the dropout rate was high. Correlations betweenOTS and clinical rating scales were adequate indicating that the test battery contains important elements of the information of well-established scales. The responsiveness and reproducibility were better for OTS than for total UPDRS

Aberrant nigral diffusion in Parkinson's disease:A longitudinal diffusion tensor imaging study

BACKGROUND: Measuring microstructure alterations with diffusion tensor imaging in PD is potentially a valuable tool to use as a biomarker for early diagnosis and to track disease progression. Previous studies have reported a specific decrease of nigral fractional anisotropy in PD. However, to date the effect of disease progression on nigral or striatal diffusion indices has not been fully explored. METHODS: We have conducted a cross-sectional and longitudinal diffusion tensor imaging study in 18 early stage, treated PD patients and 14 age-matched controls. PD patients were scanned on 2 occasions OFF medication, 19.3 months apart (standard deviation = 3.1 months). Longitudinal change of regional nigral and striatal measures of fractional anisotropy and mean diffusivity were calculated using a region-of-interest approach. RESULTS: Region-of-interest analysis demonstrated that at baseline, PD patients and controls did not differ in regard to diffusion indices in any region assessed. A significant difference of nigral fractional anisotropy and mean diffusivity between controls and PD patients at follow-up was detected and confirmed with longitudinal analysis within PD patients. Alterations in striatal regions were not detected in either group or over time. CONCLUSION: Our findings indicate that nigral diffusion measure may be a valuable measure of disease progression. In the future, larger longitudinal studies will confirm whether diffusion indices may serve as sensitive and clinically meaningful measures of disease progression in PD

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinsons disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs

Background: Continuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinsons disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG. Methods: The seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naive (N = 37), or had previous LCIG treatment for amp;lt;2 (N = 22), or amp;gt;= 2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinsons Disease Rating Scale (UPDRS), 39-item Parkinsons Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored. Results: Mean monthly costs per patient ( 8226 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naive patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations. Conclusions: Costs in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naive patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The longterm safety was consistent with the established LCIG profile. (C) 2016 AbbVie Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Funding Agencies|AbbVie Inc.</p

Additional file 1 of Patients accept therapy using embryonic stem cells for Parkinson’s disease: a discrete choice experiment

Supplementary Material

РЕКОМЕНДАЦИИ ПО ДИАГНОСТИКЕ И ЛЕЧЕНИЮ БОЛЕЗНИ НИМАННА-ПИКА ТИП С

(Pediatric Pharmacology. – 2010; 7(1):16-24)(Педиатрическая фармакология. – 2010; 7(1):16-24

Intraputamenal Cerebral Dopamine Neurotrophic Factor in Parkinson's Disease : A Randomized, Double-Blind, Multicenter Phase 1 Trial

Peer reviewe

Designing stem-cell-based dopamine cell replacement trials for Parkinson’s disease

Clinical studies of Parkinson’s disease (PD) using a dopamine cell replacment strategy have been tried for more than 30 years. The outcomes following transplantation of human fetal ventral mesencephalic tissue (hfVM) have been variable, with some patients coming off their anti-PD treatment for many years and others not responding and/or developing significant side effects, including graft-induced dyskinesia. This led to a re-appraisal of the best way to do such trials, which resulted in a new European-Union-funded allograft trial with fetal dopamine cells across several centers in Europe. This new trial, TRANSEURO (NCT01898390), is an open-label study in which some individuals in a large observational cohort of patients with mild PD who were undergoing identical assessments were randomly selected to receive transplants of hfVM. The TRANSEURO trial is currently ongoing as researchers have completed both recruitment into a large multicenter observational study of younger onset early-stage PD and transplantation of hfVM in 11 patients. While completion of TRANSEURO is not expected until 2021, we feel that sharing the rationale for the design of TRANSEURO, along with the lessons we have learned along the way, can help inform researchers and facilitate planning of transplants of dopamine-producing cells derived from human pluripotent stem cells for future clinical trials