A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease

Snow, Barry; Mulroy, Eoin; Bok, Arnold; Simpson, Mark P.; Smith, A. J.; Taylor, Kenneth M.; Lockhart, Michelle; Lam, Bb Janice; Frampton, Christopher; Schweder, Patrick; Chen, Benson; Finucane, Gregory; McMahon, Adele; Macdonald, Lorraine

doi:10.1016/j.parkreldis.2018.11.015

Cited by 34 publications

(24 citation statements)

References 20 publications

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“…In cell-based therapies, embryonic dopamine cell implant surgery entered into phase III trials by the University of Colorado Denver ( Table 2 ) (NCT00038116). The published data of the embryonic dopamine cell surgery revealed that it benefits in reversing severe PD symptoms in younger patients, but not in older patients [ 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Neuronal progenitor stem cells are collected from the adult human brain to treat PD, Alzheimer’s disease, and multiple sclerosis by Rajavithi Hospital (Thailand) (NCT00927108).…”

Section: Pd Therapeutic Strategies In Clinical Trialsmentioning

confidence: 99%

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Prasad

Hung

2021

Pharmaceuticals

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Parkinson’s disease (PD) is a progressive neurodegenerative disorder that currently has no cure, but treatments are available to improve PD symptoms and maintain quality of life. In 2020, about 10 million people worldwide were living with PD. In 1970, the United States Food and Drug Administration approved the drug levodopa as a dopamine replacement to manage PD motor symptoms; levodopa-carbidopa combination became commercialized in 1975. After over 50 years of use, levodopa is still the gold standard for PD treatment. Unfortunately, levodopa therapy-induced dyskinesia and OFF symptoms remain unresolved. Therefore, we urgently need to analyze each current clinical trial’s status and therapeutic strategy to discover new therapeutic approaches for PD treatment. We surveyed 293 registered clinical trials on ClinicalTrials.gov from 2008 to 16 June 2021. After excluded levodopa/carbidopa derivative add-on therapies, we identified 47 trials as PD treatment drugs or therapies. Among them, 19 trials are in phase I (41%), 25 trials are in phase II (53%), and 3 trials are in phase III (6%). The three phase-III trials use embryonic dopamine cell implant, 5-HT1A receptor agonist (sarizotan), and adenosine A2A receptor antagonist (caffeine). The therapeutic strategy of each trial shows 29, 5, 1, 5, 5, and 2 trials use small molecules, monoclonal antibodies, plasma therapy, cell therapy, gene therapy, and herbal extract, respectively. Additionally, we discuss the most potent drug or therapy among these trials. By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development.

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Section: Pd Therapeutic Strategies In Clinical Trialsmentioning

confidence: 99%

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Prasad

Hung

2021

Pharmaceuticals

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“…Increased albumin transfer via the BCSFB that occurs in advanced stages of the disease, indicates the barrier's disruption (Pisani et al 2012). The effect of neurotrophins derived from encapsulated porcine CPECs (termed NTCELL) considered to be a promising regenerative treatment option in PD, is still under testing for efficiency, but the phase II study, did not show improvement in tested subjects (Snow et al 2019). Very similarly, encapsulated rat CP cells were tested for regenerative treatment in another neurodegenerative disorder, Huntington disease (HD), but here the transplants showed a neuroprotective effect, with variations among different neuronal populations (Borlongan et al 2007).…”

Section: Aging Alzheimer's Disease and Other Neurodegenerative Disordersmentioning

confidence: 99%

Pathophysiology of the choroid plexus in brain diseases

Mihaljević¹,

Michalicová²,

Bhide³

2021

gpb

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The choroid plexus, located in the ventricular system of the central nervous system (CNS), obtains numerous roles critical for the proper development and operating of the CNS. The functions range from the best-known ones of the barrier and cerebrospinal fluid (CSF) producer, through participation in immune answer, 'nourishment, detoxification and reparation of the rest of the CNS. Increase number of studies point out the association between choroid plexus dysfunction, characterized by alterations in secretory, transport and barrier capabilities, and the broad spectrum of clinical conditions, as well as physiological aging. We present a brief overview of pathological states known or speculated to be connected to choroid plexus dysfunction, ranging from neurodevelopmental, to autoimmune and neurodegenerative diseases. We also cover the topic of choroid plexus tumors, as well explained involvement of the choroid plexus in pathogen invasion of the CNS, also referring to the currently actual SARS-CoV-2 infection. Finally, we have also touched conducted studies on the choroid plexus regenerative potential. With the information provided in the review we want to point out the importance and call for further research on the role of the choroid plexus in the sustainability of central nervous system health.

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“…This finding was very promising as these cells can be easily obtained and used for autologous treatment in neurodegenerative diseases. The ability of MSCs to differentiate into dopaminergic neurons was demonstrated using specific in vitro conditions in rat MSCs (Guo et al, 2005;Wang et al, 2013;Welchko et al, 2018) as well as in human MSCs (Fu et al, 2006;Trzaska et al, 2007Trzaska et al, , 2009Trzaska and Rameshwar, 2011;Singh et al, 2017;Khademizadeh et al, 2019).…”

Section: Mesenchymal Stromal Cellsmentioning

confidence: 99%

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

Salado-Manzano

Perpiñá

Straccia³

et al. 2020

Front. Cell. Neurosci.

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Neurodegenerative disorders such as Parkinson's (PD) and Huntington's disease (HD) are characterized by a selective detrimental impact on neurons in a specific brain area. Currently, these diseases have no cures, although some promising trials of therapies that may be able to slow the loss of brain cells are underway. Cell therapy is distinguished by its potential to replace cells to compensate for those lost to the degenerative process and has shown a great potential to replace degenerated neurons in animal models and in clinical trials in PD and HD patients. Fetal-derived neural progenitor cells, embryonic stem cells or induced pluripotent stem cells are the main cell sources that have been tested in cell therapy approaches. Furthermore, new strategies are emerging, such as the use of adult stem cells, encapsulated cell lines releasing trophic factors or cell-free products, containing an enriched secretome, which have shown beneficial preclinical outcomes. One of the major challenges for these potential new treatments is to overcome the host immune response to the transplanted cells. Immune rejection can cause significant alterations in transplanted and endogenous tissue and requires immunosuppressive drugs that may produce adverse effects. T-, B-lymphocytes and microglia have been recognized as the main effectors in striatal graft rejection. This review aims to summarize the preclinical and clinical studies of cell therapies in PD and HD. In addition, the precautions and strategies to ensure the highest quality of cell grafts, the lowest risk during transplantation and the reduction of a possible immune rejection will be outlined. Altogether, the wide-ranging possibilities of advanced therapy medicinal products (ATMPs) could make therapeutic treatment of these incurable diseases possible in the near future.

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A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease

Cited by 34 publications

References 20 publications

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Pathophysiology of the choroid plexus in brain diseases

Is the Immunological Response a Bottleneck for Cell Therapy in Neurodegenerative Diseases?

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