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Article ; Online: More time, more safety: is this the future optimal way for natalizumab treatment in multiple sclerosis?

Annunziata, Pasquale

Journal of neurology, neurosurgery, and psychiatry

2020 Volume 91, Issue 12, Page(s) 1251

MeSH term(s)	Humans ; Italy ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Natalizumab/adverse effects ; Treatment Outcome
Chemical Substances	Natalizumab
Language	English
Publishing date	2020-10-21
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	3087-9
ISSN	1468-330X ; 0022-3050
ISSN (online)	1468-330X
ISSN	0022-3050
DOI	10.1136/jnnp-2020-324032
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Article ; Online: Association of circulating anti-CD64 IgM levels with favourable long-term clinical outcomes in multiple sclerosis patients.

Annunziata, Pasquale / Masi, Gianni / Cioni, Chiara

Journal of neuroimmunology

2019 Volume 330, Page(s) 130–135

Abstract: Circulating levels of IgM anti-CD64, an immunosuppressive antibody recently identified in long-term stable multiple sclerosis (MS) patients, were found to fluctuate over time in MS patients. Antibody-positive patients showed a significantly lower ... ...

Abstract	Circulating levels of IgM anti-CD64, an immunosuppressive antibody recently identified in long-term stable multiple sclerosis (MS) patients, were found to fluctuate over time in MS patients. Antibody-positive patients showed a significantly lower annualized relapse rate value as well as reached sustained disability worsening and had a relapse in a significantly longer median time than those without antibody. Disease-modifying therapies (DMTs) only were the covariate influencing both the relapse occurrence and the disability accrual. Serum IgM anti-CD64 levels are associated with maintenance of clinical stability in MS and may be tested as a candidate biomarker predictive of benign course and favourable long-term response to DMTs treatment.
MeSH term(s)	Adult ; Antibodies, Anti-Idiotypic/blood ; Biomarkers/blood ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Multiple Sclerosis, Relapsing-Remitting/blood ; Multiple Sclerosis, Relapsing-Remitting/diagnosis ; Receptors, IgG/blood ; Time Factors ; Treatment Outcome
Chemical Substances	Antibodies, Anti-Idiotypic ; Biomarkers ; Receptors, IgG ; anti-IgM
Language	English
Publishing date	2019-03-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2019.03.005
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Article ; Online: Sjögren's syndrome and multiple sclerosis: Two sides of the same coin?

Masi, Gianni / Annunziata, Pasquale

Autoimmunity reviews

2016 Volume 15, Issue 5, Page(s) 457–461

Language	English
Publishing date	2016-05
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2144145-5
ISSN	1873-0183 ; 1568-9972
ISSN (online)	1873-0183
ISSN	1568-9972
DOI	10.1016/j.autrev.2016.01.013
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Article: Blood-brain barrier changes during invasion of the central nervous system by HIV-1. Old and new insights into the mechanism.

Annunziata, Pasquale

Journal of neurology

2003 Volume 250, Issue 8, Page(s) 901–906

Abstract: The mechanism underlying the early invasion of the central nervous system by HIV-1 is unclear. Here, we summarize old and new findings supporting blood-brain barrier changes during HIV and experimental simian immunodeficiency virus (SIV) infection. The ... ...

Abstract	The mechanism underlying the early invasion of the central nervous system by HIV-1 is unclear. Here, we summarize old and new findings supporting blood-brain barrier changes during HIV and experimental simian immunodeficiency virus (SIV) infection. The effect of inflammatory and toxic molecules secreted by monocytes and microglia on the functional integrity of tight junctions of brain endothelium is highlighted. Furthermore, recent findings on a possible direct role of the envelope and regulatory HIV-1 proteins (gp120, Tat, Nef) in causing the blood-brain barrier changes are reviewed. The possibility that these proteins, as circulating molecules, may bind to microvessel endothelial cells and cause blood-brain changes with no direct participation of the virus is raised. Several issues deserve further investigation and answers to these questions may provide keys for new therapeutic strategies in HIV-1 infection of the central nervous system.
MeSH term(s)	Animals ; Blood-Brain Barrier/physiology ; Central Nervous System Diseases/etiology ; Central Nervous System Diseases/virology ; Disease Models, Animal ; Gene Products, tat/metabolism ; HIV Envelope Protein gp120/metabolism ; HIV Infections/complications ; HIV-1 ; Humans ; Simian Immunodeficiency Virus/metabolism ; Simian Immunodeficiency Virus/pathogenicity ; Viral Regulatory and Accessory Proteins/metabolism ; tat Gene Products, Human Immunodeficiency Virus
Chemical Substances	Gene Products, tat ; HIV Envelope Protein gp120 ; NEF protein, SIV ; Viral Regulatory and Accessory Proteins ; tat Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2003-08
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	187050-6
ISSN	1432-1459 ; 0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
ISSN (online)	1432-1459
ISSN	0340-5354 ; 0012-1037 ; 0939-1517 ; 1619-800X
DOI	10.1007/s00415-003-1159-0
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Article ; Online: Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.

Annunziata, Pasquale / Cioni, Chiara / Mugnaini, Claudia / Corelli, Federico

Journal of neuroimmunology

2016 Volume 303, Page(s) 66–74

Abstract: COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects ... ...

Abstract	COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.
MeSH term(s)	Adamantane/analogs & derivatives ; Adamantane/pharmacology ; Adamantane/therapeutic use ; Adult ; Cannabinoid Receptor Agonists/pharmacology ; Cannabinoid Receptor Agonists/therapeutic use ; Cells, Cultured ; Cytokines/immunology ; Cytokines/metabolism ; Female ; Humans ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Male ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/immunology ; Multiple Sclerosis/metabolism ; Quinolones/pharmacology ; Quinolones/therapeutic use ; Receptor, Cannabinoid, CB2/agonists ; Receptor, Cannabinoid, CB2/immunology ; Receptor, Cannabinoid, CB2/metabolism ; T-Lymphocytes/drug effects ; T-Lymphocytes/immunology
Chemical Substances	Cannabinoid Receptor Agonists ; Cytokines ; Immunologic Factors ; N-(adamantan-1-yl)-4-oxo-1-pentyl-6-phenyl-1,4-dihydroquinoline-3-carboxamide ; Quinolones ; Receptor, Cannabinoid, CB2 ; Adamantane (PJY633525U)
Language	English
Publishing date	2016-12-23
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	8335-5
ISSN	1872-8421 ; 0165-5728
ISSN (online)	1872-8421
ISSN	0165-5728
DOI	10.1016/j.jneuroim.2016.12.009
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Article ; Online: A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

Cioni, Chiara / Tassi, Maristella / Marotta, Giuseppe / Mugnaini, Claudia / Corelli, Federico / Annunziata, Pasquale

Central nervous system agents in medicinal chemistry

2019 Volume 19, Issue 3, Page(s) 206–214

Abstract: Background: Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors.: Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2- ... ...

Abstract	Background: Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors. Aims: To test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying a high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma. Methods: Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas. Proliferation was measured in the presence or absence of COR167 with a bromodeoxyuridine (BrdU) cell proliferation ELISA assay. CB2 receptor expression was detected by western blotting. Apoptosis was assessed with phycoerythrin (PE) annexin V flow cytometry kit. TGF-beta 1 and 2 levels were analyzed in culture supernatants with commercial ELISAs. Results: COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with a significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures. Conclusion: These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas.
MeSH term(s)	Adamantane/analogs & derivatives ; Adamantane/chemistry ; Adamantane/pharmacology ; Apoptosis/drug effects ; Apoptosis/physiology ; Cannabinoid Receptor Agonists/chemistry ; Cannabinoid Receptor Agonists/pharmacology ; Cannabinoids/chemistry ; Cannabinoids/pharmacology ; Cell Proliferation/drug effects ; Cell Proliferation/physiology ; Dose-Response Relationship, Drug ; Glioma/metabolism ; Glioma/pathology ; Humans ; Quinolones/chemistry ; Quinolones/pharmacology ; Receptor, Cannabinoid, CB2/agonists ; Transforming Growth Factor beta/antagonists & inhibitors ; Transforming Growth Factor beta/metabolism ; Tumor Cells, Cultured
Chemical Substances	Cannabinoid Receptor Agonists ; Cannabinoids ; N-(adamantan-1-yl)-4-oxo-1-pentyl-6-phenyl-1,4-dihydroquinoline-3-carboxamide ; Quinolones ; Receptor, Cannabinoid, CB2 ; Transforming Growth Factor beta ; Adamantane (PJY633525U)
Language	English
Publishing date	2019-10-09
Publishing country	United Arab Emirates
Document type	Journal Article
ZDB-ID	2227560-5
ISSN	1875-6166 ; 1871-5249
ISSN (online)	1875-6166
ISSN	1871-5249
DOI	10.2174/1871524919666190923154351
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Article ; Online: Symptomatic cranial neuralgias in multiple sclerosis: clinical features and treatment.

De Santi, Lorenzo / Annunziata, Pasquale

Clinical neurology and neurosurgery

2012 Volume 114, Issue 2, Page(s) 101–107

Abstract: In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of ... ...

Abstract	In multiple sclerosis, neuropathic pain is a frequent condition, negatively influencing the overall quality of life. Cranial neuralgias, including trigeminal, glossopharyngeal neuralgias, as well as occipital neuralgia, are typical expression of neuropathic pain. Neuralgias are characterised by paroxysmal painful attacks of electric shock-like sensation, occurring spontaneously or evoked by innocuous stimuli in specific trigger areas. In multiple sclerosis, demyelination in the centrally myelinated part of the cranial nerve roots plays an important role in the origin of neuralgic pain. These painful syndromes arising in multiple sclerosis are therefore considered "symptomatic", in contrast to classic cranial neuralgias, in which no cause other than a neurovascular contact is identified. At this time, the evidence on the management of symptomatic cranial neuralgias in multiple sclerosis is fragmentary and a comprehensive review addressing this topic is still lacking. For that reason, treatment is often based on personal clinical experience as well as on anecdotal reports. The aim of this review is to critically summarise the latest findings regarding the pathogenesis, the diagnosis, the instrumental evaluation and the medical as well as neurosurgical treatment of symptomatic trigeminal, glossopharyngeal and occipital neuralgia in multiple sclerosis, providing useful insights for neurologists and neurosurgeons and a broad range of specialists potentially involved in the treatment of these painful syndromes.
MeSH term(s)	Adrenal Cortex Hormones/therapeutic use ; Cranial Nerve Diseases/etiology ; Cranial Nerve Diseases/surgery ; Cranial Nerve Diseases/therapy ; Glossopharyngeal Nerve Diseases/etiology ; Glossopharyngeal Nerve Diseases/surgery ; Glossopharyngeal Nerve Diseases/therapy ; Humans ; Multiple Sclerosis/complications ; Neuralgia/etiology ; Neuralgia/surgery ; Neuralgia/therapy ; Neurosurgical Procedures ; Trigeminal Neuralgia/etiology ; Trigeminal Neuralgia/surgery ; Trigeminal Neuralgia/therapy
Chemical Substances	Adrenal Cortex Hormones
Language	English
Publishing date	2012-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	193107-6
ISSN	1872-6968 ; 0303-8467
ISSN (online)	1872-6968
ISSN	0303-8467
DOI	10.1016/j.clineuro.2011.10.044
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Article ; Online: Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients.

Annunziata, Pasquale / Cioni, Chiara / Masi, Gianni / Tassi, Maristella / Marotta, Giuseppe / Severi, Sauro

Scientific reports

2018 Volume 8, Issue 1, Page(s) 15371

Abstract: There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [ ... ...

Abstract	There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [occludin (OCLN), claudin-5 (CLN-5) and zonula occludens-1 (ZO-1)] levels, sphingosine-1 phosphate 1 (S1P
MeSH term(s)	Adult ; Biomarkers/blood ; Cell Movement ; Chemotaxis ; Female ; Fingolimod Hydrochloride/pharmacology ; Gene Expression Regulation/drug effects ; Humans ; Immunosuppressive Agents/pharmacology ; In Vitro Techniques ; Leukocytes, Mononuclear/drug effects ; Longitudinal Studies ; Male ; Multiple Sclerosis/blood ; Multiple Sclerosis/drug therapy ; Multiple Sclerosis/pathology ; Prospective Studies ; Receptors, Lysosphingolipid/blood ; Tight Junction Proteins/blood
Chemical Substances	Biomarkers ; Immunosuppressive Agents ; Receptors, Lysosphingolipid ; Tight Junction Proteins ; Fingolimod Hydrochloride (G926EC510T)
Language	English
Publishing date	2018-10-18
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-33672-9
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Article ; Online: Longitudinal quantitative assessment of macula during therapy with fingolimod in relapsing-remitting multiple sclerosis.

Fruschelli, Mario / Capozzoli, Marco / Gelmi, Maria Chiara / Masi, Gianni / Annunziata, Pasquale

International ophthalmology

2018 Volume 39, Issue 4, Page(s) 777–781

Abstract: Purpose: Fingolimod is the first oral drug approved for treatment of relapsing-remitting multiple sclerosis (RR-MS), and it has potential macular side effects. Despite the qualitative evidence of macular oedema under treatment, longitudinal quantitative ...

Abstract	Purpose: Fingolimod is the first oral drug approved for treatment of relapsing-remitting multiple sclerosis (RR-MS), and it has potential macular side effects. Despite the qualitative evidence of macular oedema under treatment, longitudinal quantitative assessment is lacking. To address this issue, we measured macular volume and central foveal thickness in a cohort of MS patients on fingolimod over 12 months of treatment. Methods: Central foveal thickness (CFT) and total macular volume (TMV) were longitudinally recorded with spectral-domain optical coherence tomography in a cohort of 23 RR-MS patients treated with fingolimod at baseline, 3, 6 and 12 months. OCT parameters were analysed considering previous history of optic neuritis (ON). Comparison of means was performed with variance analysis (ANOVA). Results: Macular oedema occurred in none of the patients. Comparing both groups of patients (with and without previous ON), no statistically significant difference was found during the follow-up both for CFT and TMV (p = 0.99 and p = 0.96, respectively) although a slight early but not significant TMV reduction was detected. Conclusions: In our cohort, therapy with fingolimod did not cause any change in CFT and TMV in MS patients during a 12-month follow-up independent of previous ON.
MeSH term(s)	Adult ; Analysis of Variance ; Female ; Fingolimod Hydrochloride/adverse effects ; Fingolimod Hydrochloride/therapeutic use ; Fovea Centralis/pathology ; Humans ; Immunosuppressive Agents/adverse effects ; Immunosuppressive Agents/therapeutic use ; Macula Lutea/pathology ; Macular Edema/chemically induced ; Macular Edema/pathology ; Male ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/drug therapy ; Tomography, Optical Coherence
Chemical Substances	Immunosuppressive Agents ; Fingolimod Hydrochloride (G926EC510T)
Language	English
Publishing date	2018-03-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	800087-6
ISSN	1573-2630 ; 0165-5701
ISSN (online)	1573-2630
ISSN	0165-5701
DOI	10.1007/s10792-018-0870-x
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Article ; Online: Severe aquaporin-4 IgG-positive neuromyelitis optica spectrum disorder with short myelitis lesion and favourable outcome.

Masi, Gianni / Cioni, Chiara / Arrigucci, Umberto / Cerase, Alfonso / Annunziata, Pasquale

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2015 Volume 36, Issue 10, Page(s) 1925–1927

MeSH term(s)	Anti-Inflammatory Agents/therapeutic use ; Aquaporin 4/immunology ; Female ; Humans ; Immunoglobulin G/blood ; Magnetic Resonance Imaging ; Methylprednisolone/therapeutic use ; Myelitis/complications ; Myelitis/drug therapy ; Neuromyelitis Optica/complications ; Neuromyelitis Optica/drug therapy ; Neuromyelitis Optica/immunology ; Treatment Outcome ; Young Adult
Chemical Substances	AQP4 protein, human ; Anti-Inflammatory Agents ; Aquaporin 4 ; Immunoglobulin G ; Methylprednisolone (X4W7ZR7023)
Language	English
Publishing date	2015-10
Publishing country	Italy
Document type	Case Reports ; Letter
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-015-2277-z
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