Grafting of Encapsulated Dopamine-Secreting Cells in Parkinson's Disease: Long-Term Primate Study

The transplantation of encapsulated dopamine-secreting cells into the striatum represents one potential means of treating Parkinson's disease. The present study investigated the ability of encapsulated PC12 cells, which are derived from rat pheochromocytoma, to supply L-dopa and dopamine into the primate brain in the long term and to effect functional improvement in the animals. Following polymer encapsulation, PC12 cells were transplanted into the striatum of hemiparkinsonian monkeys. The secretion of L-dopa and dopamine from the encapsulated cells, the morphology of these cells, the histology of the host striatum surrounding the capsule, and functional changes in the host animals were examined 1, 6, and 12 months after transplantation. Analysis of retrieved capsules revealed that the PC12 cells survived and continued to release L-dopa and dopamine even 12 months after transplantation. The histological response of the host brain surrounding the capsules was minimal and there were no signs of immunological rejection or tumor formation. The physical condition of the host animals was good for 12 months, and hematologic and cerebrospinal fluid analysis revealed that no animals suffered from infection or immunological reaction. These PC12 cell-grafted monkeys showed improvements in hand movements after transplantation, effects that lasted for at least 12 months. These results further support the potential use of this approach for the treatment of Parkinson's disease.

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Faculty Opinions recommendation of Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727492597.793530605 ◽

2017 ◽

Author(s):

Laurent Villard

Keyword(s):

Parkinson’S Disease ◽

Gene Therapy ◽

Parkinson's Disease ◽

Gene Therapy Trial ◽

Long Term Follow Up ◽

Therapy Trial

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Neurobehavioral Consequences Associated with Long Term Tramadol Utilization and Pathological Mechanisms

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666191112124435 ◽

2020 ◽

Vol 18 (10) ◽

pp. 758-768 ◽

Cited By ~ 2

Author(s):

Khadga Raj ◽

Pooja Chawla ◽

Shamsher Singh

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Serotonin Syndrome ◽

Dopamine Synthesis ◽

Synthetic Analog

: Tramadol is a synthetic analog of codeine used to treat pain of moderate to severe intensity and is reported to have neurotoxic potential. At therapeutic dose, tramadol does not cause major side effects in comparison to other opioid analgesics, and is useful for the management of neurological problems like anxiety and depression. Long term utilization of tramadol is associated with various neurological disorders like seizures, serotonin syndrome, Alzheimer’s disease and Parkinson’s disease. Tramadol produces seizures through inhibition of nitric oxide, serotonin reuptake and inhibitory effects on GABA receptors. Extensive tramadol intake alters redox balance through elevating lipid peroxidation and free radical leading to neurotoxicity and produces neurobehavioral deficits. During Alzheimer’s disease progression, low level of intracellular signalling molecules like cGMP, cAMP, PKC and PKA affect both learning and memory. Pharmacologically tramadol produces actions similar to Selective Serotonin Reuptake Inhibitors (SSRIs), increasing the concentration of serotonin, which causes serotonin syndrome. In addition, tramadol also inhibits GABAA receptors in the CNS has been evidenced to interfere with dopamine synthesis and release, responsible for motor symptoms. The reduced level of dopamine may produce bradykinesia and tremors which are chief motor abnormalities in Parkinson’s Disease (PD).

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The mechanistic role of thymoquinone in Parkinson's disease: focus on neuroprotection in pre-clinical studies

Current Molecular Pharmacology ◽

10.2174/1874467214666210105140944 ◽

2021 ◽

Vol 14 ◽

Author(s):

Mohammad Najim Uddin ◽

Mohammad Injamul Hoq ◽

Israt Jahan ◽

Shafayet Ahmed Siddiqui ◽

Chayan Dhar Clinton ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Studies ◽

Nigella Sativa ◽

Biological Effects ◽

Neuroprotective Activity ◽

Substantia Nigra Pars Compacta ◽

Movement Difficulties

: Thymoquinone (TQ) is one of the leading phytochemicals, which is abundantly found in Nigella sativa L. seeds. TQ exhibited various biological effects such as antioxidant, anti-inflammatory, antimicrobial, and anti-tumoral in several pre-clinical studies. Parkinson's disease (PD) is a long-term neurodegenerative disease with movement difficulties, and the common feature of neurodegeneration in PD patients is caused by dopaminergic neural damage in the substantia nigra pars compacta. The neuroprotective activity of TQ has been studied in various neurological disorders. TQ-mediated neuroprotection against PD yet to be reported in a single frame; therefore, this review is intended to narrate the potentiality of TQ in the therapy of PD. TQ has been shown to protect against neurotoxins via amelioration of neuroinflammation, oxidative stress, apoptosis, thereby protects neurodegeneration in PD models. TQ could be an emerging therapeutic intervention in PD management, but mechanistic studies have been remained to be investigated to clarify its neuroprotective role.

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Focal Subthalamic Atrophy After Long‐Term Deep Brain Stimulation in Parkinson's Disease

Movement Disorders ◽

10.1002/mds.28653 ◽

2021 ◽

Author(s):

Ellen Gelpi ◽

Christine Haberler ◽

Alexander Micko ◽

Andrea Polt ◽

Andreas Amon ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Deep Brain

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Long term mortality of patients with Parkinson’s disease treated with deep brain stimulation in a reference center

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2021.106486 ◽

2021 ◽

Vol 202 ◽

pp. 106486

Author(s):

Ana Luísa Rocha ◽

Ana Oliveira ◽

Cláudia Sousa ◽

Pedro Monteiro ◽

Maria José Rosas ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Reference Center ◽

Deep Brain ◽

Long Term Mortality

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Extradural Motor Cortex Stimulation in Parkinson’s Disease: Long-Term Clinical Outcome

Brain Sciences ◽

10.3390/brainsci11040416 ◽

2021 ◽

Vol 11 (4) ◽

pp. 416

Author(s):

Carla Piano ◽

Francesco Bove ◽

Delia Mulas ◽

Enrico Di Stasio ◽

Alfonso Fasano ◽

...

Keyword(s):

Quality Of Life ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Cortex ◽

Clinical Outcome ◽

Motor Cortex Stimulation ◽

Dopaminergic Therapy

Previous investigations have reported on the motor benefits and safety of chronic extradural motor cortex stimulation (EMCS) for patients with Parkinson’s disease (PD), but studies addressing the long-term clinical outcome are still lacking. In this study, nine consecutive PD patients who underwent EMCS were prospectively recruited, with a mean follow-up time of 5.1 ± 2.5 years. As compared to the preoperatory baseline, the Unified Parkinson’s Disease Rating Scale (UPDRS)-III in the off-medication condition significantly decreased by 13.8% at 12 months, 16.1% at 18 months, 18.4% at 24 months, 21% at 36 months, 15.6% at 60 months, and 8.6% at 72 months. The UPDRS-IV decreased by 30.8% at 12 months, 22.1% at 24 months, 25% at 60 months, and 36.5% at 72 months. Dopaminergic therapy showed a progressive reduction, significant at 60 months (11.8%). Quality of life improved by 18.0% at 12 months, and 22.4% at 60 months. No surgical complication, cognitive or behavioral change occurred. The only adverse event reported was an infection of the implantable pulse generator pocket. Even in the long-term follow-up, EMCS was shown to be a safe and effective treatment option in PD patients, resulting in improvements in motor symptoms and quality of life, and reductions in motor complications and dopaminergic therapy.

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PARKINSON’S DISEASE — LONG-TERM THERAPY WITH LEVODOPA

InPharma ◽

10.1007/bf03287873 ◽

1975 ◽

Vol 10 (1) ◽

pp. 8-8

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Term Therapy ◽

Long Term Therapy

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Evidence for Early and Regular Physical Therapy and Exercise in Parkinson's Disease

Seminars in Neurology ◽

10.1055/s-0041-1725133 ◽

2021 ◽

Author(s):

Terry D. Ellis ◽

Cristina Colón-Semenza ◽

Tamara R. DeAngelis ◽

Cathi A. Thomas ◽

Marie-Hélène Saint Hilaire ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Physical Therapy ◽

Secondary Prevention ◽

Medical Management ◽

Long Term Outcomes ◽

High Prevalence ◽

Growing Body ◽

Prevention Model

AbstractAdvances in medical management of Parkinson's disease (PD) have resulted in living longer with disability. Although disability worsens over the course of the disease, there are signs of disability even in the early stages. Several studies reveal an early decline in gait and balance and a high prevalence of nonmotor signs in the prodromal period that contribute to early disability. There is a growing body of evidence revealing the benefits of physical therapy and exercise to mitigate motor and nonmotor signs while improving physical function and reducing disability. The presence of early disability coupled with the benefits of exercise suggests that physical therapy should be initiated earlier in the disease. In this review, we present the evidence revealing early disability in PD and the effectiveness of physical therapy and exercise, followed by a discussion of a secondary prevention model of rehabilitation to reduce early disability and optimize long-term outcomes.

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