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19 results for “progressive multifocal leukoencephalopathy”
A more accurate risk biomarkers recognition for Progressive Multifocal Leukoencephalopathy (PML) caused by Polyomavirus JC in patients with multiple sclerosis during treatment with disease-modifying therapies (DMTs): an ongoing clinical challenge.
<p>The therapeutic scenario for the treatment of MS has recently been characterized by a veritable revolution, which has included the introduction, for the first time, of drug treatment guidelines and the entry, in the therapeutic landscape of the last decade, of numerous new drugs that, in varying but significantly relevant ways, have proven capable of modifying the course of the disease (Disease-Modifying Therapies - DMTs). <br> While the arsenal of available drugs has resulted in advances in efficacy and selectivity, it has also exposed them to the danger of side effects, potentially serious and in some cases even fatal. Among the most important side effects, complications of infectious origin, characterized by cases of viral infection/reactivation, as in the case of JCPyV, the etiologic agent of PML, are the most represented. This study, based on the follow-up of MS patients treated with different DMTs, contributes to implementing the data in the literature regarding a greater understanding of the risks related to the administration of these drugs and more appropriate monitoring of MS treatment. The risk of JCPyV reactivation with Fingolimod and Dimethyl fumarate is lower than the risk of viral reactivation associated with natalizumab.<br> In light of the data obtained, it is possible to conclude that, in the case of natalizumab, testing for JC viruria would seem to be more useful in identifying those patients with a JCPyV-specific humoral response that is not yet detectable. In addition, our results, draw attention to the importance of analyzing the NCCR rearrangements of JCPyV. Indeed, the particular rearrangements found in plasma and PBMCs of patients with RRMS treated with natalizumab could represent an alert of neuroinvasiveness in order to detect early those patients with a higher risk of developing PML. In the case of dimethyl fumarate, it seems likely that monitoring of lymphopenia would identify a higher risk group of patients in whom alternative therapy should be sought. Prolonged lymphopenia, with absolute lymphocyte counts less than 750 lymphocytes/mL, might be the major risk factor for PML although, a greater risk might lie in the loss of CD8+ cells that are crucial for JCPyV control.<br> For fingolimod, this strategy cannot be applied because the number of circulating lymphocytes decreases while the actual lymphocyte function appears largely normal therefore, monitoring viruria and viremia along with identification of the neurotrophic variant of the virus seems a more exploitable means for risk stratification.</p> <p>In conclusion, the results of this study can be considered directly transferable to the National Health System in that, both the monitoring of JCPyV reactivation by viruria and the sequence analysis of viral NCCR and host immune set-up could play the role of translatable biomarkers in clinical practice in order to assess the risk of PML onset. In addition to improving risk stratification of this disease, these biomarkers of viral reactivation and pathogenicity could facilitate timely diagnosis, optimizing the use of health care resources and contributing to the reduction of direct and indirect costs of MS disease.</p> <p>Prezioso Carla was supported by the Italian Ministry of Health (Starting Grant: SG-2018-12366194).</p>
Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML)
ClinicalTrials.gov study NCT00746941. IPD Sharing: Not stated. Countries: 5. Publications: 1.
Comparison of Anti HIV Drugs Used Alone or in Combination With Cytosine Arabinoside to Treat Progressive Multifocal Leukoencephalopathy (PML) in HIV-Infected Patients
ClinicalTrials.gov study NCT00001048. IPD Sharing: Not stated. Countries: 1. Publications: 4.
Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells
ClinicalTrials.gov study NCT02694783. IPD Sharing: Not stated. Countries: 1. Publications: 1.
A Study to Evaluate the Use of Cidofovir (an Experimental Drug) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in AIDS Patients
ClinicalTrials.gov study NCT00000945. IPD Sharing: Not stated. Countries: 1. Publications: 1.
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
ClinicalTrials.gov study NCT01730131. IPD Sharing: Not stated. Countries: 1. Publications: 3.
Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection
ClinicalTrials.gov study NCT06276504. IPD Sharing: YES. Countries: 1. Publications: 0.
Genetics of Progressive Multifocal Leukoencephalopathy and Acquired Immunodeficiency Syndrome
ClinicalTrials.gov study NCT00342602. IPD Sharing: Not stated. Countries: 1. Publications: 1.
NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy
ClinicalTrials.gov study NCT04781309. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Role of Inflammation in Progressive Multifocal Leukoencephalopathy (PML)
ClinicalTrials.gov study NCT01132053. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy
ClinicalTrials.gov study NCT04453917. IPD Sharing: NO. Countries: 1. Publications: 0.
TOPIK Study: A Study to Report Progressive Multifocal Leukoencephalopathy and Other Serious Opportunistic Infections in Natalizumab Treated Participants
ClinicalTrials.gov study NCT05236777. IPD Sharing: YES. Countries: 1. Publications: 0.
Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy
ClinicalTrials.gov study NCT05849467. IPD Sharing: UNDECIDED. Countries: 1. Publications: 0.
Genetic Evaluation of Natalizumab-Treated Patients With Progressive Multifocal Leukoencephalopathy
ClinicalTrials.gov study NCT01211639. IPD Sharing: Not stated. Countries: 2. Publications: 0.
Observational Study on Characteristics and Survival Correlates of Progressive Multifocal Leukoencephalopathy (PML) in Italy
ClinicalTrials.gov study NCT06594614. IPD Sharing: NO. Countries: 1. Publications: 0.
A Pilot Study of the Efficacy of Recombinant Alpha Interferon (IFN-A2b) and Zidovudine (AZT) in the Treatment of Progressive Multifocal Leukoencephalopathy (PML) Complicating HIV-1 Infection
ClinicalTrials.gov study NCT00002270. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Safety and Effectiveness of Topotecan HCl to Treat HIV-Infected Patients With AIDS-Related Progressive Multifocal Leukoencephalopathy (PML)
ClinicalTrials.gov study NCT00002395. IPD Sharing: Not stated. Countries: 1. Publications: 0.
Retrospective Study of the Survival of Patients Suffering From Hiv-related Progressive Multifocal Leukoencephalopathy
ClinicalTrials.gov study NCT02895581. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Adoptive Transfer of JC Virus-Specific T Lymphocytes for the Treatment of Progressive Multifocal Leukoencephalopathy
<p>The dataset reports the clinical and paraclinical characteristics of the 9 patients treated with T cell therapy included in the final article, including gender, age at diagnosis, underlying hematological conditions, neurological symptoms at diagnosis, JCV viral load in the cerebrospinal fluid, number of T cell infusions, and neurological outcome following treatment. Nuclear magnetic resonance data are not reported.</p> <p>The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV) -specific T cell therapy in a cohort of hematological patients with PML.</p> <p>9 patients with a diagnosis of "definite PML" who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides.</p> <p>In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. None of the patients experienced treatment-related adverse events.</p>
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