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.

scholarly journals Role of Serotonin Neurons in L-DOPA- and Graft-Induced Dyskinesia in a Rat Model of Parkinson's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Eunju Shin ◽  
Elisabetta Tronci ◽  
Manolo Carta
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Work ◽  
Serotonin System ◽  
Serotonin Neurons ◽  
Advanced Stages ◽  
Ventral Mesencephalic ◽  
The One ◽  
Patients Experience

L-DOPA, the most effective drug to treat motor symptoms of Parkinson's disease, causes abnormal involuntary movements, limiting its use in advanced stages of the disease. An increasing body of evidence points to the serotonin system as a key player in the appearance of L-DOPA-induced dyskinesia (LID). In fact, exogenously administered L-DOPA can be taken up by serotonin neurons, converted to dopamine and released as a false transmitter, contributing to pulsatile stimulation of striatal dopamine receptors. Accordingly, destruction of serotonin fibers or silencing serotonin neurons by serotonin agonists could counteract LID in animal models. Recent clinical work has also shown that serotonin neurons are present in the caudate/putamen of patients grafted with embryonic ventral mesencephalic cells, producing intense serotonin hyperinnervation. These patients experience graft-induced dyskinesia (GID), a type of dyskinesia phenotypically similar to the one induced by L-DOPA but independent from its administration. Interestingly, the 5-HT1Areceptor agonist buspirone has been shown to suppress GID in these patients, suggesting that serotonin neurons might be involved in the etiology of GID as for LID. In this paper we will discuss the experimental and clinical evidence supporting the involvement of the serotonin system in both LID and GID.

scholarly journals Low dose niacin versus placebo in the treatment of Parkinson’s Disease:  A Randomized Controlled Trial

2021 ◽  
Author(s):  
Chandramohan Wakade ◽  
Raymond Chong ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Banabihari Giri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Open Label ◽  
Double Blind ◽  
One Year ◽  
Time Point

Abstract BackgroundParkinson’s Disease (PD) patients have lower niacin levels compared to their spouses. The main objective was to study low-dose daily niacin supplementation versus placebo on motor symptoms in Parkinson’s disease subjects.MethodsA randomized, placebo-controlled, double-blind, single-center clinical trial in Parkinson’s disease patients was performed in Augusta, GA, between September 2016 to September 2019. Randomized participants were 47 PD patients who received either low-dose niacin (N = 21 ) or placebo (N = 26) for the first six months (mean age 68.4 SD, 8.7; mean duration of disease 5.8 SD 4.9; H&Y scores between 0.5 to 4; 64% subjects were Veterans). The Veterans Affairs Pharmacy generated the randomized sequence. After the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, six months, and one year of treatment. The main outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue.Results39 subjects were analyzed with low-dose niacin (N = 18) and placebo (N = 21) for the completion of the first six months (randomized, double-blind), and 31 subjects were analyzed for the completion of the next six months (open-label) with low-dose niacin (N = 14) and placebo (N = 17). Niacin treatment was not tolerated by two subjects. The baseline mean UPDRS III score was 21.3 ± 15.8 for the niacin group and 22.4 ± 11.8 for placebo. The change with six months of placebo was 0.05 [95% CI, -2.4 to 2.32], and niacin was 1.06 [95% CI, -3.68 to 1.57]. From six to twelve months, the average UPDRS III score decreased for the placebo group by 4.58 [95% CI, -0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83]. Eight subjects withdrew from the study before the 6-month time point and eight more before the one-year time point due to voluntary discontinuation, flushing, or inability to continue (SARS-CoV-2 shut-down).ConclusionLow-dose niacin supplementation may be helpful as an adjunct therapy in improving motor function in PD.Trial registrationClinicaltrials.gov, NCT03462680. Registered 12 March 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03462680?term=gpr109A&draw=2&rank=1

scholarly journals Levodopa-carbidopa enteral suspension in advanced Parkinson’s disease: clinical evidence and experience

2016 ◽  
Vol 10 (3) ◽  
pp. 171-187 ◽  
Author(s):  
Johan Virhammar ◽  
Dag Nyholm
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Evidence ◽  
Motor Fluctuations ◽  
Small Scale ◽  
Double Blind Study ◽  
Open Label ◽  
Double Blind ◽  
Duration Of Action ◽  
Substantial Impact

The duration of action of oral levodopa becomes shorter as Parkinson’s disease (PD) progresses. Patients with advanced PD may develop potentially disabling motor fluctuations and abnormal involuntary movement (dyskinesia), which cannot be managed with optimized oral or transdermal PD medications. The progressively worsening symptoms can have a substantial impact on the patient quality of life (QoL). Levodopa–carbidopa intestinal gel (LCIG) is delivered continuously via a percutaneous endoscopic gastrostomy with a jejunal extension (PEG-J). LCIG is licensed for the treatment of levodopa-responsive advanced PD in individuals experiencing severe motor fluctuations and dyskinesia when available combinations of antiparkinsonian medications have not given satisfactory results. Initial evidence for the efficacy and tolerability of LCIG came from a number of small-scale studies, but recently, three prospective studies have provided higher quality evidence. A 12-week double-blind comparison of LCIG with standard levodopa therapy, a 52-week open-label study extension of the double-blind study, and a 54-week open-label safety study, demonstrated significant improvements in ‘off’ time and ‘on’ time without troublesome dyskinesia, and QoL measures that were maintained in the longer term. There are also observations that LCIG may be effective treatment for nonmotor symptoms (NMS) although the evidence is limited. There is a need for further research on the efficacy of LCIG in reducing NMS, dyskinesia and improving QoL. This review surveys the clinical evidence for the effectiveness and tolerability of LCIG in the management of advanced PD and highlights some practical considerations to help optimize treatment.

Atypical Antipsychotic Drugs in the Treatment of Parkinson’s Disease

2011 ◽  
Vol 24 (6) ◽  
pp. 534-540 ◽  
Author(s):  
Joseph H. Friedman
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Function ◽  
Antipsychotic Drugs ◽  
Psychotic Symptoms ◽  
Open Label ◽  
Double Blind ◽  
Pharmacological Mechanism ◽  
Motor Problems ◽  
Home Placement

Parkinson’s disease (PD) patients often develop psychotic symptoms that severely affect quality of life and limit the use of medications to ameliorate motor symptoms. Psychotic symptoms are a major cause for nursing home placement. While these symptoms do not always require treatment, they often do but antipsychotic drugs all share the common pharmacological mechanism of blocking dopamine D2 receptors which may worsen motor problems in this very vulnerable population. Double blind, placebo controlled trials (DBPCT) have shown that clozapine is effective at controlling the psychotic symptoms at doses far below those used in schizophrenia, without worsening motor function, even improving tremor. DBPCT have demonstrated that olanzapine worsens motor function without improving psychosis. Quetiapine has been shown in DBPCT to be free of motor side effects in PD patients but not effective, whereas many open label studies have indicated that quetiapine is effective. The other atypical have been the subjects of conflicting open label reports. The effects of the atypicals in PD psychosis is reviewed.

scholarly journals Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations

2021 ◽  
Author(s):  
Atsushi Takeda ◽  
Ryosuke Takahashi ◽  
Yoshio Tsuboi ◽  
Masahiro Nomoto ◽  
Tetsuya Maeda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Motor Fluctuations ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Off Time

AbstractThe double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease) study in Japanese levodopa-treated patients with Parkinson’s disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [− 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [− 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [− 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

scholarly journals Low-Dose Niacin Supplementation Improves Motor Function in US Veterans with Parkinson’s Disease: A Single-Center, Randomized, Placebo-Controlled Trial

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1881
Author(s):  
Chandramohan Wakade ◽  
Raymond Chong ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Banabihari Giri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Function ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Trial ◽  
Randomized Study ◽  
Secondary Outcome ◽  
Open Label ◽  
Double Blind

A six-month double-blind, placebo-controlled randomized study was conducted to ascertain whether low-dose daily niacin supplementation would improve motor symptoms in Parkinson’s disease (PD) patients. A total of 47 PD patients were assigned to receive low-dose niacin or a placebo. At the end of the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, after six months, and after one year of treatment. The primary outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue. Niacin treatment was well-tolerated by forty-five subjects. The mean [95% CI] change in UPDRS III scores at six months of placebo was −0.05 [95% CI, −2.4 to 2.32], and niacin was −1.06 [95% CI, −3.68 to 1.57]. From six to twelve months when both groups received open-label niacin supplementation, the average UPDRS III scores significantly decreased for the placebo group by 4.58 [95% CI, −0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83] points. Low-dose niacin supplementation is a well-tolerated adjunct therapy and may improve motor function in PD when taken over a longer period.

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