Toward a Phase III Multicenter Study of Fetal Ventral Mesencephalic Transplants in Patients with Late-Stage Parkinson's Disease

2003 ◽  
pp. 31-44 ◽  
Author(s):  
Marc Peschanski ◽  
Gilles Defer ◽  
Sophie Dethy ◽  
Philippe Hantraye ◽  
Marc Levivier ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multicenter Study ◽  
Late Stage ◽  
Phase Iii ◽  
Ventral Mesencephalic

Progression of Parkinson’s Disease and Unmet Needs in Mid- to Late-stage Patients

2015 ◽  
Vol 10 (2) ◽  
pp. 182
Author(s):  
Heinz Reichmann ◽  
Paolo Barone ◽  
Werner Poewe ◽  
◽  
◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Stage ◽  
Unmet Needs ◽  
Early Stage ◽  
Early Morning ◽  
Motor Fluctuations ◽  
Phase Iii ◽  
Motor Symptoms ◽  
Beneficial Effects

In early-stage Parkinson’s disease (PD), dopaminergic treatment is highly effective in controlling motor symptoms. However, as the disease progresses, other symptoms and comorbidities need to be addressed, such as suboptimal motor control, emerging motor complications (e.g. nocturnal and early-morning akinesia/tremor, early wearing-off and dyskinesia), emerging levodopa-resistant motor symptoms, increasing non-motor symptoms and treatment of non-dopaminergic symptoms. Despite these unmet needs, no new therapies for PD have been introduced into routine clinical practice over the past 10 years. Safinamide is a new oral therapy that has both dopaminergic and non-dopaminergic mechanisms of action. In phase III clinical trials, safinamide has demonstrated significant clinical benefits in patients with mid- to late-stage PD experiencing motor fluctuations as an add-on therapy to levodopa and other PD medication versus those treated only on an optimised PD therapy. This includes improvements in daily ON time, improvements in motor function and beneficial effects on dyskinesia that have been studied in patients for up to 2 years. Safinamide is well tolerated, and it is a new and unique agent in the armamentarium of treatments for patients with mid- to late-stage PD experiencing motor fluctuations.

scholarly journals Factors Associated with Health‐Related Quality of Life in Late‐Stage Parkinson's Disease

2021 ◽  
Author(s):  
Kristina Rosqvist ◽  
Per Odin ◽  
Stefan Lorenzl ◽  
Wassilios G. Meissner ◽  
Bastiaan R. Bloem ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Late Stage ◽  
Health Related Quality ◽  
Factors Associated ◽  
Related Quality ◽  
Health Related

scholarly journals Foetal Cell Transplantation for Parkinson’s Disease: Focus on Graft-Induced Dyskinesia

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Elisabetta Tronci ◽  
Camino Fidalgo ◽  
Manolo Carta
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Transplantation ◽  
Open Label ◽  
Double Blind ◽  
Clinical Investigations ◽  
Serotonin Neurons ◽  
Ventral Mesencephalic ◽  
Preclinical And Clinical Studies ◽  
Foetal Cell

Transplantation of dopamine- (DA-) rich foetal ventral mesencephalic cells emerged as a promising therapy for Parkinson’s disease (PD), as it allowed significant improvement of motor symptoms in several PD patients in open-label studies. However, double-blind clinical trials have been largely disappointing. The general agreement in the field is that the lack of standardization of tissue collection and preparation, together with the absence of postsurgical immunosuppression, played a key role in the failure of these studies. Moreover, a further complication that emerged in previous studies is the appearance of the so-called graft-induced dyskinesia (GID), in a subset of grafted patients, which resembles dyskinesia induced by L-DOPA but in the absence of medication. Preclinical evidence pointed to the serotonin neurons as possible players in the appearance of GID. In agreement, clinical investigations have shown that grafted tissue may contain a large number of serotonin neurons, in the order of half of the DA cells; moreover, the serotonin 5-HT1A receptor agonist buspirone has been found to produce significant dampening of GID in grafted patients. In this paper, we will review the recent preclinical and clinical studies focusing on cell transplantation for PD and on the mechanisms underlying GID.

Intranigral Grafts of Fetal Ventral Mesencephalic Tissue in Adult 6-Hydroxydopamine-Lesioned Rats can Induce Behavioral Recovery

1997 ◽  
Vol 6 (3) ◽  
pp. 267-276 ◽  
Author(s):  
R.E. Johnston ◽  
Jill B. Becker
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cyclosporine A ◽  
Ventral Mesencephalon ◽  
Behavioral Recovery ◽  
Treatment Conditions ◽  
Movement Sequence ◽  
Ventral Mesencephalic ◽  
6 Hydroxydopamine ◽  
Disease Specific

Intrastriatal grafts of fetal ventral mesencephalon in rats with unilateral 6-hydroxydopamine lesions can reduce and even reverse rotational behavior in response to direct and indirect dopamine agonists. These grafts can ameliorate deficits on simple spontaneous behaviors, but do not improve complex behaviors that require the skilled integration of the use of both paws. We report here that rats with grafts into the DA-depleted substantia nigra, that receive cyclosporine A, can experience recovery on spontaneous behaviors that mimic those observed in Parkinson's disease. Specific cyclosporine A treatment conditions can differentially affect whether intranigral grafts normalize paw use during initiation or termination of a movement sequence. These findings may have important implications for the treatment of Parkinson's disease.

scholarly journals Safety of Levodopa-Carbidopa Intestinal Gel Treatment in Patients with Advanced Parkinson’s Disease Receiving ≥2000 mg Daily Dose of Levodopa

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Cindy Zadikoff ◽  
Werner Poewe ◽  
James T. Boyd ◽  
Lars Bergmann ◽  
Horia Ijacu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Phase Iii ◽  
High Dose ◽  
Double Blind Study ◽  
Dosage Group ◽  
Continuous Administration ◽  
Advanced Parkinson’S Disease ◽  
Off Time

Background. Levodopa-carbidopa intestinal gel (LCIG) provides continuous levodopa administration and clinical benefits to patients with advanced Parkinson’s disease (PD). This report evaluates long-term safety and efficacy of high-dose LCIG in PD patients. Methods. Data were collected from several prospective, phase III clinical studies and an observational registry. The phase III program (N = 412) included four multicenter studies: a 12-week, randomized, double-blind study and three open-label studies extending ≥12 months. GLORIA (N = 375) was a 24-month, multicountry, observational registry. LCIG safety (adverse effects (AEs)/adverse drug reactions (ADRs)) and efficacy (modified Unified Parkinson’s Disease Rating Scale (UPDRS) part IV item 32 and 39 scores for “On” time with dyskinesia and “Off” time) were assessed in patients who received ≥2000 mg/day vs <2000 mg/day LCIG. Results. A total of 72 of 412 (17.5%) patients required dosages ≥2000 mg/day LCIG in the phase III program and 47 of 375 (12.5%) patients in GLORIA. Baseline demographics and disease severity were similar between dosage groups with more men in the high-dosage group. Compared with the <2000 mg/day dosage group, patients requiring ≥2000 mg/day LCIG had higher rates of AEs/ADRs including polyneuropathy; improvements in “Off” time and discontinuations due to AEs were similar between dosage groups and lower for discontinuations due to ADRs reported in GLORIA. Conclusions. Patients who require ≥2000 mg/day LCIG exhibited a safety profile comparable to the established safety/tolerability of LCIG with similar clinical improvements. Higher AEs were noted but within what is accepted for LCIG. Continuous administration of LCIG is beneficial to advanced PD patients who require very high doses of levodopa.

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