Tropical spastic paraparesis

Summary

Tropical spastic paraparesis (MONDO:0008039) is a disease with 8 GWAS associations across 1 studies and 10 clinical trials. Top therapeutic interventions include pentoxifylline and teriflunomide. A subtype of human T-lymphotropic virus 1 infectious disease — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

• Prevalence: Unknown (Worldwide)
• GWAS associations: 8
• Clinical trials: 10

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	tropical spastic paraparesis
Mondo ID	MONDO:0008039
EFO	EFO:0007527
MeSH	D015493
OMIM	159580
Orphanet	289326
DOID	DOID:321
ICD-10-CM	G04.1
ICD-11	1043229589
SNOMED CT	714279000
UMLS	C0030481
MedGen	18298
GARD	0008208
MedDRA	10044696
Is cancer (heuristic)	no

Also known as: ham · HAM/TSP · ham/TSP · HTLV-1 associated myelopathy/tropical spastic paraparesis · HTLV-1-associated myelopathy/tropical spastic paraparesis · Human T-cell leukaemia virus type 1 associated myelopathy/tropical spastic paraparesis · Human T-cell leukemia virus type 1 associated myelopathy/tropical spastic paraparesis · Human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis · Human T-lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis · myelopathy, HTLV-1-associated · tropical spastic paraparesis (formerly) · tropical spastic paraplegia · TSP

Data availability: 8 GWAS associations (1 study) · 1 cell line.

Disease family

This is a subtype of human T-lymphotropic virus 1 infectious disease. 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 etiologic mechanism › disease of primarily extrinsic mechanism › infectious disease › viral infectious disease › human T-lymphotropic virus 1 infectious disease › tropical spastic paraparesis

Related subtypes (1): adult T-cell leukemia/lymphoma

Genetics & variants

GWAS landscape

8 GWAS associations across 1 studies. Top hits map to 7 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2517451	2e-09	HCG21, MUCL3, SFTA2	C	2.69
rs3130933	5e-09	TCF19	T	2.44
rs28895103	1e-08	HLA-DRA - HLA-DRB9	G	0.44
rs2523554	3e-08	HLA-B	C	1.83
rs13195509	3e-07	BTN2A1	G	0.37
rs3093983	4e-07	MCCD1	G	1.86
rs2647012	5e-07	HLA-DQB1 - MTCO3P1	T	0.56
rs9461416	2e-06	H2BC15 - H2BC16P	G	0.51

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90026455	Penova M	2021	731	0	Genome wide association study of HTLV-1-associated myelopathy/tropical spastic paraparesis in the Japanese population.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	2
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	5

MAF distribution

Bucket	Variants
common (>=0.05)	5
low_freq (0.01-0.05)	3
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	3
missense_variant	2
intergenic_variant	2
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2517451	6	30946974	C>A,G,T	0.04	intron_variant	HCG21, MUCL3, SFTA2	2e-09	Tier 4: intronic/intergenic
rs3130933	6	31164308	T>A,C,G	0.04	3_prime_UTR_variant	TCF19	5e-09	Tier 2: splice/UTR
rs28895103	6	32451687	G>A	0.05	intron_variant	HLA-DRA - HLA-DRB9	1e-08	Tier 4: intronic/intergenic
rs2523554	6	31364052	C>A,G,T	0.11	intron_variant	HLA-B	3e-08	Tier 4: intronic/intergenic
rs13195509	6	26463432	G>A	0.03	missense_variant	BTN2A1	3e-07	Tier 1: coding
rs3093983	6	31529148	G>A,C,T	0.08	missense_variant	MCCD1	4e-07	Tier 1: coding
rs2647012	6	32696681	T>A,C,G	0.17	intergenic_variant	HLA-DQB1 - MTCO3P1	5e-07	Tier 4: intronic/intergenic
rs9461416	6	27858082	G>A	0.05	intergenic_variant	H2BC15 - H2BC16P	2e-06	Tier 4: intronic/intergenic

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 for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Mogamulizumab	Phase 3 (in late-stage trials)
Valproic Acid	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Cyclosporine, Infliximab, Lamivudine, Tamibarotene, Zidovudine.

Clinical trials & evidence

Clinical trials

Clinical trials: 10.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	5
PHASE3	1
PHASE2	1
PHASE1/PHASE2	1
EARLY_PHASE1	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01472263	PHASE3	COMPLETED	Use of Pentoxifylline in Human T-lymphotropic Virus Type-1 (HTLV-1) Diseases
NCT04799288	PHASE1/PHASE2	RECRUITING	Teriflunomide in HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
NCT00001785	PHASE2	COMPLETED	Recombinant Human Interferon Beta-1a (Avonex) for the Treatment of Patients With HTLV-1-Associated Myelopathy (HAM)
NCT02961712	PHASE1	UNKNOWN	Immunotherapy of Natural Killer(NK) Cells in Human T Lymphotropic Virus Type 1(HTLV-1) Associated Myelopathy(HAM)
NCT02655471	EARLY_PHASE1	COMPLETED	Effect of Raltegravir in Patients With Acute Tropical Spastic Paraparesis - Human T-Lymphotropic Virus 1 Infection
NCT00001778	Not specified	RECRUITING	Evaluation of Patients With HAM/TSP
NCT00001156	Not specified	COMPLETED	Assessment of Patients With Multiple Sclerosis (MS)
NCT00034723	Not specified	COMPLETED	MRI Brain Studies in Patients With HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis
NCT01651819	Not specified	COMPLETED	Urological Physical Therapy in HTLV-1 With Urinary Symptoms
NCT04830319	Not specified	COMPLETED	Pilates Method in People With HAM/TSP

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PENTOXIFYLLINE	4	1
TERIFLUNOMIDE	4	1