Immunotherapy against Prion Disease

Ma, Yanbing; Ma, Jiyan

doi:10.3390/pathogens9030216

Cited by 19 publications

(17 citation statements)

References 141 publications

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“…Studies using ICSM35, an anti-PrP antibody with an epitope of PrP 95-105, has also been shown to result in cognitive benefits, without toxicity, in a rat Tg model of AD with amyloid plaques (Zhang et al, 2017). Passive and active immunization targeting PrP is emerging as a potential therapeutic approach for prion disease and current experience suggests that this can be done safely, but with certain caveats that include consideration of epitopes targeted, dosage, and routes of administration (Wisniewski and Goñi, 2018;Ma and Ma, 2020).…”

Section: Discussionmentioning

confidence: 99%

Passive Immunization With a Novel Monoclonal Anti-PrP Antibody TW1 in an Alzheimer’s Mouse Model With Tau Pathology

Boutajangout

Zhang

Kim

et al. 2021

Front. Aging Neurosci.

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Neurofibrillary tangles (NFTs) are a major pathologic hallmark of Alzheimer’s disease (AD). Several studies have shown that amyloid β oligomers (Aβo) and tau oligomers mediate their toxicity, in part, via binding to cellular prion protein (PrPC) and that some anti-PrP antibodies can block this interaction. We have generated a novel monoclonal anti-PrP antibody (TW1) and assessed the efficacy of passive immunization with it in a mouse model of AD with extensive tau pathology: hTau/PS1 transgenic (Tg) mice. These mice were injected intraperitoneally once a week with TW1 starting at 5 months of age. Behavior was assessed at 8 months of age and brain tissue was subsequently harvested for analysis of treatment efficacy at 9 months. Mice treated with TW1 did not show any significant difference in sensorimotor testing including traverse beam, rotarod, and locomotor activity compared to controls. Significant cognitive benefits were observed with the novel object recognition test (ORT) in the immunized mice (two-tailed, t-test p = 0.0019). Immunized mice also showed cognitive benefits on the closed field symmetrical maze (day 1 two-tailed t-test p = 0.0001; day 2 two-tailed t-test p = 0.0015; day 3 two-tailed t-test p = 0.0002). Reduction of tau pathology was observed with PHF-1 immunohistochemistry in the piriform cortex by 60% (two-tailed t-test p = 0.01) and in the dentate gyrus by 50% (two-tailed t-test p = 0.02) in animals treated with TW1 compared to controls. There were no significant differences in astrogliosis or microgliosis observed between treated and control mice. As assessed by Western blots using PHF-1, the TW1 therapy reduced phosphorylated tau pathology (two-tailed t-test p = 0.03) and improved the ratio of pathological soluble tau to tubulin (PHF1/tubulin; two-tailed t-test p = 0.0006). Reduction of tau pathology also was observed using the CP13 antibody (two-tailed t-test p = 0.0007). These results indicate that passive immunization with the TW1 antibody can significantly decrease tau pathology as assessed by immunohistochemical and biochemical methods, resulting in improved cognitive function in a tau transgenic mouse model of AD.

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Section: Discussionmentioning

confidence: 99%

Passive Immunization With a Novel Monoclonal Anti-PrP Antibody TW1 in an Alzheimer’s Mouse Model With Tau Pathology

Boutajangout

Zhang

Kim

et al. 2021

Front. Aging Neurosci.

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“…Immunotherapy is also a promising approach against prion disease because it may block PrP Sc and/or PrP C , hindering the conversion. Protective effects of active immunization studies have not proven sufficient to date [ 255 ]. Passive immunization has had more promising results.…”

Section: Viruses Commonly Associated With Cns Infection In Brazilmentioning

confidence: 99%

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Sousa

Santos

Paula

et al. 2021

Viruses

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Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.

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“…During the progression of prion disease, the infectious protein PrP sc aggregates and becomes resistant to proteinase digestion. This is followed by PrP sc -seeded conversion of PrP c into PrP sc , therefore, resulting in the high accumulation of PrP sc in an individual, which leads to neurodegeneration and the clinical manifestation of the disease [194]. This disease is classified as rare both in the progression and manifestation [195].…”

Section: Prion Diseasementioning

confidence: 99%

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

et al. 2020

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With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.

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Immunotherapy against Prion Disease

Cited by 19 publications

References 141 publications

Passive Immunization With a Novel Monoclonal Anti-PrP Antibody TW1 in an Alzheimer’s Mouse Model With Tau Pathology

Passive Immunization With a Novel Monoclonal Anti-PrP Antibody TW1 in an Alzheimer’s Mouse Model With Tau Pathology

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals

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