Translational research for Parkinson׳s disease: The value of pre-clinical primate models

Badin, Romina Aron; Vadori, Marta; Cozzi, Emanuele; Hantraye, Philippe

doi:10.1016/j.ejphar.2015.03.038

Cited by 11 publications

(2 citation statements)

References 102 publications

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“…Here, some of the mechanisms underlying DA neuronal cell death are summarized ( Figure 1A), based on neuropathological studies either from animal models or from human postmortem samples (Dauer and Przedborski, 2003;Hartmann, 2004). Several animal models of PD are available to study the disease (Blesa and Przedborski, 2014;Aron Badin et al, 2015), but none of them replicates human PD etiopathogenesis, nor accurately represents the anatomic organization of the human brain.…”

Section: Parkinson's Diseasementioning

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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Section: Parkinson's Diseasementioning

confidence: 99%

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

Salado-Manzano

Perpiñá

Straccia³

et al. 2020

Front. Cell. Neurosci.

Self Cite

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“…However, Alzheimer disease and PD are considered specific to Homo sapiens (13–15). While there are useful animal models of PD including MPTP and alpha-synuclein-overexpressing transgenic mouse models, which may recapitulate important clinical features of the human disorders (5, 14), especially in aged monkeys (16, 17), no spontaneous akinetic-rigid syndrome is known to occur in wild mammals including non-human primates.…”

Section: Pd Is Specifically Humanmentioning

confidence: 99%

Parkinson Disease: An Evolutionary Perspective

Ruiz

Espay

2017

Front. Neurol.

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There are two central premises to this evolutionary view of Parkinson disease (PD). First, PD is a specific human disease. Second, the prevalence of PD has increased over the course of human history. Several lines of evidence may explain why PD appears to be restricted to the human species. The major manifestations of PD are the consequence of degeneration in the dopamine-synthesizing neurons of the mesostriatal neuronal pathway. It is of note the enormous expansion of the human dopamine mesencephalic neurons onto the striatum compared with other mammals. Hence, an evolutionary bottle neck was reached with the expansion of the massive nigrostriatal axonal arborization. This peculiar nigral overload may partly explain the selective fragility of the human dopaminergic mesencephalic neurotransmission and the unique presence of PD in humans. On the other hand, several facts may explain the increasing prevalence of PD over the centuries. The apparently low prevalence of PD before the twentieth century may be related to the shorter life expectancy and survival compared to present times. In addition, changes in lifestyle over the course of human history might also account for the increasing burden of PD. Our hunter-gatherers ancestors invested large energy expenditure on a daily basis, a prototypical physical way of life for which our genome remains adapted. Technological advances have led to a dramatic reduction of physical exercise. Since the brain release of neurotrophic factors (including brain-derived neurotrophic factor) is partially exercise related, the marked reduction in exercise may contribute to the increasing prevalence of PD.

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Nonhuman Primate Models of Huntington’s Disease and Their Application in Translational Research

Badin

2018

Methods in Molecular Biology

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Huntington's disease (HD) is a monogenic, autosomal dominant inherited fatal disease that affects 1 in 10,000 people worldwide. Given its unique genetic characteristics, HD would appear as one of the most straightforward neurodegenerative diseases to replicate in animal models. Indeed, mutations in the HTT gene have been used to generate a variety of animal models that display differential pathologies and have significantly increased our understanding of the pathological mechanisms of HD. However, decades of efforts have also shown the complexity of recapitulating the human condition in other species. Here we describe the three different types of models that have been generated in nonhuman primate species, stating their advantages and limitations and attempt to give a critical perspective of their translational value to test the efficacy of novel therapeutic strategies. Obtaining construct, phenotypic, and predictive validity has proven to be challenging in most animal models of human diseases. In HD in particular, it is hard to assess the predictive validity of a new therapeutic strategy when no effective "benchmark" treatment is available in the clinic. In this light, only phenotypic/face validity and construct validity are discussed.

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Translational research for Parkinson׳s disease: The value of pre-clinical primate models

Cited by 11 publications

References 102 publications

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

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

Parkinson Disease: An Evolutionary Perspective

Nonhuman Primate Models of Huntington’s Disease and Their Application in Translational Research

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