Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive...
Multiple SclerosisProgressive Multifocal LeukoencephalopathyBackground: Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are disorders that affect the central nervous system (CNS). The CNS includes the brain, spinal cord, and optic nerves. Both diseases can cause muscle weakness and impair vision, speech, and coordination. Researchers are working to better understand how MS and PML affect the CNS. Objective: To test whether an experimental radioactive tracer (minibody) can help positron emission tomography (PET) scans detect certain immune cells in the CNS of people with MS and PML. Eligibility: People aged 18 years and older with MS or PML. Design: Participants will come to the clinic for at least 3 visits over 4 to 6 weeks. Participants will undergo testing. They will have a physical and neurological exam. They will have blood tests and tests of their heart function. They will have a magnetic resonance imaging (MRI) scan of the brain. They may have a spinal tap: Their lower back will be numbed, and a needle will be inserted between the bones of the spine to withdraw fluid from around the spinal cord. Minibody is given through a tube with a needle placed in a vein in the arm. This takes 5 to 10 minutes. Participants will have heart function tests before and after receiving the minibody. Participants will return the next day for the PET scan. They will lie on a table that moves through a doughnut-shaped machine. This scan will take about 1 hour. Participants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.
NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia...
Progressive Multifocal LeukoencephalopathyBackground: Progressive multifocal leukoencephalopathy (PML) is a brain infection. It is caused by a virus. PML can happen in people with a weakened immune system. PML is associated with cognitive and visual impairment as well as motor and speech disturbances. There is no treatment for PML. Researchers want to see if a new drug can help. Objective: To see if the drug NT-I7 can help increase lymphocyte numbers, which may help control PML infection. Eligibility: Adults ages 18 and older with PML who are enrolled in Protocol #13-N-0017. Design: Participants will be screened under Protocol #13-N-0017. Participants will have a 7-day inpatient stay, outpatient visits, and follow-up phone calls. Participants will have a medical history and physical exam. They will give urine samples. Blood will be drawn from an arm vein or through an intravenous (IV) catheter. Participants will get up to 3 doses of NT-I7. It will be given by injection into the muscle. Participants will have lumbar punctures ( spinal taps ). A thin needle will be inserted into the spinal canal in the lower back. Cerebrospinal fluid will be removed. X-ray may be used to guide the procedure. Participants will have magnetic resonance imaging (MRI) of the brain. The MRI scanner is a metal cylinder surrounded by a magnetic field. During MRIs, participants will lie on a table that slides in and out of the scanner. Soft padding or a coil will be placed around their head. They will get gadolinium, a contrast agent, through an IV catheter. Participation will last for 12 to 19 months.
Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy...
Progressive Multifocal LeukoencephalopathyProgressive multifocal leukoencephalopathy (PML) is a rare viral infection of the central nervous system (CNS) occurring in immunocompromised patients. Recovery of JC virus (JCV) specific T cell immune responses is the only available therapeutic option. JCV may use immune checkpoint inhibitory pathways to evade immune responses. The aim of this project is to determine whether T cell expression of immune checkpoint molecules is correlated to antiviral T cell responses, control of JCV replication and PML outcome. Immune checkpoint blockade by reversing T cell exhaustion may represent a therapeutic perspective for PML.
A Phase 2 Study Evaluating JCPyV-specific T Cell Therapy for PML
Progressive Multifocal LeukoencephalopathyThis is a randomized, double-blinded, Phase 2 trial in patients with PML due to JCPyV. Patients will receive treatment with a matched virus-specific T-cell product (CE VST01-JC) or placebo, and will then be monitored for response to therapy.
TOPIK Study: A Study to Report Progressive Multifocal Leukoencephalopathy and Other Serious Opportunistic...
Multiple SclerosisThe primary objective of the study is to estimate the incidence of progressive multifocal leukoencephalopathy (PML) and serious adverse events (SAEs) of other opportunistic infections (OIs) among all participants taking natalizumab. The secondary objectives of the study are to estimate the incidence of SAEs, to estimate the incidence of SAEs among participant subgroups defined by demographic and clinical factors (age, gender, duration of treatment, pregnancy, breastfeeding), to characterize and estimate incidences of malignancies, hypersensitivity reactions and John Cunningham Virus (JCV) positivity among all participants taking natalizumab, and to count and describe pregnancies and breastfeeding among participants previously exposed to natalizumab.
Natural History Study of Progressive Multifocal Leukoencephalopathy (PML)
Progressive Multifocal LeukoencephalopathyBackground: - Progressive multifocal leukoencephalopathy (PML) is a severe viral infection of the brain. It is caused by JC virus. Many people have this virus in their bodies all their life, but it is usually kept in check by their immune system. If the immune system does not work right because of a disease or medication, the virus becomes active and can damage cells in the brain. Not much is known about PML or how it affects the immune system. Researchers want to study people with PML to better understand the natural history of the disease. Objectives: - To study the natural history of PML. Eligibility: - Individuals at least 2 years of age who have PML. Design: Participants will be screened with a physical exam, medical history, and imaging studies. Participants will have several visits to the National Institutes of Health Clinical Center. There will be an initial visit, monthly visits for the next 6 months, a 12-month visit, and possible visits afterward. At the initial visit, participants will give blood, urine, and spinal fluid samples. They will also have neurological tests and imaging studies of the brain. For the next five visits, participants will give blood and urine samples. They will also have neurological tests and imaging studies of the brain. The 6-month and 12-month visits will repeat the tests from the initial visit. Other optional procedures include bone marrow samples and skin biopsies. Additional blood tests and imaging studies may be performed. Treatment will not be provided as part of this study.
Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS)
Immune Reconstitution Inflammatory SyndromeLeukoencephalopathy1 moreThe objectives of this study are to explore the effects of administering high-dose corticosteroids to participants who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab as measured by time-course change in functional status based on Karnofsky Performance Status Index through 6 months following the completion of plasma exchange (PLEX; or equivalent), survival at 6 months following the completion of PLEX (or equivalent), and incidence and severity of adverse events (AEs) and serious adverse events (SAEs); to characterize the evolution of immune reconstitution inflammatory syndrome (IRIS) as measured by time course changes in Global Clinical Impression of Improvement (GCI-I), Symbol Digit Modalities Test (SDMT), brain magnetic resonance imaging (MRI), magnetoencephalography (MEG), chemokines, cytokines, C-reactive protein (CRP), John Cunningham virus (JCV) load and cell count in cerebrospinal fluid (CSF); and to characterize the time course elimination of serum natalizumab concentrations in the study population following the last PLEX (or equivalent) procedure.
Tysabri Observational Cohort Study - Multiple Sclerosis (MS) Registries
Progressive Multifocal LeukoencephalopathyThe primary purpose of this study is to estimate the incidence of progressive multifocal leukoencephalopathy (PML) among patients who switched to Tysabri from disease modifying therapies (DMTs), including newer DMTs (including fingolimod, dimethyl fumarate and teriflunomide) and the established DMTs (interferon beta and glatiramer acetate). Researchers will also look to estimate the incidence of other serious opportunistic infections among patients who switch to Tysabri from newer DMTs (including fingolimod, dimethyl fumarate and teriflunomide) and the established DMTs (interferon beta and glatiramer acetate)
Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy...
Progressive Multifocal LeukoencephalopathyThe primary objective of the study was to explore whether mefloquine can delay or stop progression of progressive multifocal leukoencephalopathy (PML) as measured by JC virus (human polyomavirus or JCV) deoxyribonucleic acid (DNA) levels in cerebrospinal fluid (CSF). The secondary objective of the study was to explore whether mefloquine can delay or stop progression of PML based on neurological deterioration, magnetic resonance imaging (MRI) measures of brain lesion evolution or the formation of new lesions, and mortality.
Safety and Effectiveness of Topotecan HCl to Treat HIV-Infected Patients With AIDS-Related Progressive...
HIV InfectionsLeukoencephalopathy1 moreThe purpose of this study is to see if it is safe and effective to give topotecan through a vein to treat HIV-infected patients with PML, an opportunistic (AIDS-related) infection caused by a virus that infects brain tissue and causes damage to the brain and the spinal cord. Topotecan fights HIV and the JC virus (the virus that causes PML) in laboratory experiments.