Progressive multifocal leukoencephalopathy
disease diseaseOn this page
Also known as leukoencephalopathy, progressive multifocalPMLprogressive multifocal leukoencephalitis
Summary
Progressive multifocal leukoencephalopathy (MONDO:0016318) is a disease and 24 clinical trials. Top therapeutic interventions include cidofovir anhydrous, brincidofovir, and didanosine. A subtype of infectious encephalitis — broader associated-gene and molecular evidence is on the parent page (see Disease family below).
At a glance
- Prevalence: <1 / 1 000 000 (Sweden) [Orphanet-validated]
- Phenotypes (HPO): 35
- Clinical trials: 24
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Annual incidence | <1 / 1 000 000 | 0.068 | Sweden | Validated |
| Annual incidence | 1-9 / 1 000 000 | 0.11 | France | Validated |
Signs & symptoms
Clinical features (HPO)
35 HPO clinical features (Orphanet curated; top 35 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0000707 | Abnormality of the nervous system | Very frequent (80-99%) |
| HP:0002721 | Immunodeficiency | Very frequent (80-99%) |
| HP:0002921 | Abnormality of the cerebrospinal fluid | Very frequent (80-99%) |
| HP:0004302 | Functional motor deficit | Very frequent (80-99%) |
| HP:0007305 | CNS demyelination | Very frequent (80-99%) |
| HP:0031392 | Abnormal proportion of CD4 T cells | Very frequent (80-99%) |
| HP:0100706 | Abnormality of the oligodendroglia | Very frequent (80-99%) |
| HP:0100707 | Abnormal astrocyte morphology | Very frequent (80-99%) |
| HP:0000505 | Visual impairment | Frequent (30-79%) |
| HP:0001260 | Dysarthria | Frequent (30-79%) |
| HP:0001268 | Mental deterioration | Frequent (30-79%) |
| HP:0002066 | Gait ataxia | Frequent (30-79%) |
| HP:0002167 | Abnormality of speech or vocalization | Frequent (30-79%) |
| HP:0002315 | Headache | Frequent (30-79%) |
| HP:0003474 | Somatic sensory dysfunction | Frequent (30-79%) |
| HP:0003690 | Limb muscle weakness | Frequent (30-79%) |
| HP:0004374 | Hemiplegia/hemiparesis | Frequent (30-79%) |
| HP:0005415 | Decreased proportion of CD8-positive T cells | Frequent (30-79%) |
| HP:0010549 | Weakness due to upper motor neuron dysfunction | Frequent (30-79%) |
| HP:0100543 | Cognitive impairment | Frequent (30-79%) |
| HP:0000639 | Nystagmus | Occasional (5-29%) |
| HP:0000751 | Personality changes | Occasional (5-29%) |
| HP:0001123 | Visual field defect | Occasional (5-29%) |
| HP:0001250 | Seizure | Occasional (5-29%) |
| HP:0001300 | Parkinsonism | Occasional (5-29%) |
| HP:0002321 | Vertigo | Occasional (5-29%) |
| HP:0002381 | Aphasia | Occasional (5-29%) |
| HP:0004377 | Hematological neoplasm | Occasional (5-29%) |
| HP:0012246 | Oculomotor nerve palsy | Occasional (5-29%) |
| HP:0025479 | Self-neglect | Occasional (5-29%) |
| HP:0030516 | Homonymous hemianopia | Occasional (5-29%) |
| HP:0000651 | Diplopia | Very rare (<1-4%) |
| HP:0001287 | Meningitis | Very rare (<1-4%) |
| HP:0001310 | Dysmetria | Very rare (<1-4%) |
| HP:0003401 | Paresthesia | Very rare (<1-4%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | progressive multifocal leukoencephalopathy |
| Mondo ID | MONDO:0016318 |
| EFO | EFO:0007455 |
| MeSH | D007968 |
| Orphanet | 217260 |
| DOID | DOID:643 |
| ICD-10-CM | A81.2 |
| ICD-11 | 902939755 |
| NCIT | C26815 |
| SNOMED CT | 22255007 |
| UMLS | C0023524 |
| MedGen | 7327 |
| GARD | 0007468 |
| MedDRA | 10036807 |
| NORD | 1616 |
| Is cancer (heuristic) | no |
Also known as: leukoencephalopathy, progressive multifocal · PML · progressive multifocal leukoencephalitis
Data availability: 5 cell lines.
Disease family
This is a subtype of infectious encephalitis. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.
Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › encephalomyelitis › encephalitis › infectious encephalitis › progressive multifocal leukoencephalopathy
Related subtypes (9): primary amebic meningoencephalitis, granulomatous amebic encephalitis, syphilitic encephalitis, Kluver-Bucy syndrome, viral encephalitis, acute necrotizing encephalopathy of childhood, Hendra virus infection, Mycoplasma encephalitis, postinfectious encephalitis
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
No tiered GWAS variants or ClinVar records for this disease.
Genes & proteins
No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).
Function
No pathway enrichment — requires an associated-gene cohort.
Therapeutics
Drugs indicated or in trials for this disease
No drug has an approved disease-direct ChEMBL indication for this disease.
1 drug in clinical trials for this disease (phase 2–3, investigational): efficacy not established — a trial record, not an indication.
| Drug | Highest phase |
|---|---|
| Pembrolizumab | Phase 2 |
Clinical trials & evidence
Clinical trials
Clinical trials: 24.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 12 |
| PHASE2 | 6 |
| EARLY_PHASE1 | 2 |
| PHASE4 | 1 |
| PHASE2/PHASE3 | 1 |
| PHASE1/PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01211665 | PHASE4 | TERMINATED | Corticosteroids for Immune Reconstitution Inflammatory Syndrome (IRIS) |
| NCT06276504 | PHASE2/PHASE3 | NOT_YET_RECRUITING | Pembrolizumab in Progressive Multifocal Leukoencephalopathy (PML) in Immunocompromised Patients Without HIV Infection |
| NCT07511049 | PHASE2 | RECRUITING | Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study |
| NCT00001048 | PHASE2 | COMPLETED | Comparison of Anti HIV Drugs Used Alone or in Combination With Cytosine Arabinoside to Treat Progressive Multifocal Leukoencephalopathy (PML) in HIV-Infected Patients |
| NCT00002395 | PHASE2 | COMPLETED | Safety and Effectiveness of Topotecan HCl to Treat HIV-Infected Patients With AIDS-Related Progressive Multifocal Leukoencephalopathy (PML) |
| NCT00120367 | PHASE2 | COMPLETED | Early Intensification of Antiretroviral Therapy Including Enfuvirtide in HIV-1-Related Progressive Multifocal Leucoencephalopathy (ANRS125) |
| NCT00746941 | PHASE1/PHASE2 | TERMINATED | Study to Explore the Effect of Mefloquine in Participants With Progressive Multifocal Leukoencephalopathy (PML) |
| NCT04091932 | PHASE2 | UNKNOWN | Treatment of PD-1 Inhibitor in AIDS-associated PML |
| NCT05541549 | PHASE2 | UNKNOWN | A Phase 2 Study Evaluating JCPyV-specific T Cell Therapy for PML |
| NCT05849467 | PHASE1 | RECRUITING | Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy |
| NCT02694783 | EARLY_PHASE1 | COMPLETED | Adoptive Cellular Immunotherapy for Progressive Multifocal Leukoencephalopathy With Ex Vivo Generated Polyomavirus-Specific T-Cells |
| NCT04781309 | EARLY_PHASE1 | COMPLETED | NT-I7, a Long-Acting Recombinant IL-7 Molecule, as an Immune Reconstitution Strategy for Lymphopenia in Patients With Progressive Multifocal Leukoencephalopathy |
| NCT01730131 | Not specified | RECRUITING | Natural History Study of Progressive Multifocal Leukoencephalopathy (PML) |
| NCT07512518 | Not specified | RECRUITING | Observational Cohort Study of Chronic Viral Infection in the Central Nervous System |
| NCT00000945 | Not specified | COMPLETED | A Study to Evaluate the Use of Cidofovir (an Experimental Drug) for the Treatment of Progressive Multifocal Leukoencephalopathy (PML) in AIDS Patients |
| NCT00002270 | Not specified | COMPLETED | 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 |
| NCT00002274 | Not specified | COMPLETED | A Study of ddI in Patients With AIDS Who Become Sicker While Taking Zidovudine |
| NCT01132053 | Not specified | COMPLETED | Role of Inflammation in Progressive Multifocal Leukoencephalopathy (PML) |
| NCT01211639 | Not specified | TERMINATED | Genetic Evaluation of Natalizumab-Treated Patients With Progressive Multifocal Leukoencephalopathy |
| NCT02004444 | Not specified | COMPLETED | JC Virus Reactivation in Multiple Sclerosis |
| NCT02895581 | Not specified | COMPLETED | Retrospective Study of the Survival of Patients Suffering From Hiv-related Progressive Multifocal Leukoencephalopathy |
| NCT03399981 | Not specified | COMPLETED | Tysabri Observational Cohort Study - Multiple Sclerosis (MS) Registries |
| NCT04453917 | Not specified | COMPLETED | Dynamics of T Cell Expression of Immune Checkpoint Molecules in Progressive Multifocal Leukoencephalopathy |
| NCT06594614 | Not specified | COMPLETED | Observational Study on Characteristics and Survival Correlates of Progressive Multifocal Leukoencephalopathy (PML) in Italy |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| CIDOFOVIR ANHYDROUS | 4 | 2 |
| BRINCIDOFOVIR | 4 | 1 |
| DIDANOSINE | 4 | 1 |
| ENFUVIRTIDE | 4 | 1 |
| INTERFERON ALFA-2B | 4 | 1 |
| MEFLOQUINE | 4 | 1 |
| METHYLPREDNISOLONE | 4 | 1 |
| NATALIZUMAB | 4 | 1 |
| PREDNISOLONE | 4 | 1 |
| PROBENECID | 4 | 1 |
| TOPOTECAN | 4 | 1 |
| ZALCITABINE | 4 | 1 |
| EFINEPTAKIN ALFA | 2 | 1 |
| CHEMBL39066 | 0 | 1 |
| (S,R)-MEFLOQUINE | 0 | 1 |