Machado-Joseph disease

Summary

Machado-Joseph disease (MONDO:0007182) is a disease caused by ATXN3 (GenCC Definitive), with 6 cohort genes (8 GWAS associations across 1 studies) and 30 clinical trials. Top therapeutic interventions include phenylbutanoic acid, lithium carbonate, and varenicline.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Causal gene: ATXN3 (GenCC Definitive)
• Cohort genes: 6
• GWAS associations: 8
• ClinVar variants: 9
• Phenotypes (HPO): 16
• Clinical trials: 30

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000	1.5	Worldwide	Validated
Point prevalence	1-9 / 100 000	1	Portugal	Validated
Point prevalence	1-9 / 100 000	5.5	Japan	Validated

Signs & symptoms

Clinical features (HPO)

16 HPO clinical features (Orphanet curated; top 16 by frequency):

HPO ID	Term	Frequency
HP:0000520	Proptosis	Very frequent (80-99%)
HP:0000590	Progressive external ophthalmoplegia	Very frequent (80-99%)
HP:0000639	Nystagmus	Very frequent (80-99%)
HP:0000651	Diplopia	Very frequent (80-99%)
HP:0000750	Delayed speech and language development	Very frequent (80-99%)
HP:0001260	Dysarthria	Very frequent (80-99%)
HP:0001332	Dystonia	Very frequent (80-99%)
HP:0001347	Hyperreflexia	Very frequent (80-99%)
HP:0002071	Abnormality of extrapyramidal motor function	Very frequent (80-99%)
HP:0002073	Progressive cerebellar ataxia	Very frequent (80-99%)
HP:0002312	Clumsiness	Very frequent (80-99%)
HP:0003202	Skeletal muscle atrophy	Very frequent (80-99%)
HP:0007256	Abnormal pyramidal sign	Very frequent (80-99%)
HP:0001605	Vocal cord paralysis	Occasional (5-29%)
HP:0001751	Abnormal vestibular function	Occasional (5-29%)
HP:0004370	Abnormality of temperature regulation	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	Machado-Joseph disease
Mondo ID	MONDO:0007182
MeSH	D017827
OMIM	109150
Orphanet	98757
DOID	DOID:1440
NCIT	C84830
SNOMED CT	91952008
UMLS	C0024408
MedGen	9841
GARD	0006801
NORD	1389
Is cancer (heuristic)	no

Also known as: autosomal dominant striatonigral degeneration · Azorean disease of the nervous system · Machado disease · Machado-Joseph disease · MJD · Nigro-spino-dentatal degeneration with nuclear ophthalmoplegia · SCA3 · spinocerebellar ataxia 3 · spinocerebellar ataxia type 3 · spinocerebellar atrophy type 3

Data availability: 9 ClinVar variants · 8 GWAS associations (1 study) · 3 GenCC gene-disease records · 42 cell lines.

Disease family

An umbrella term covering 4 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › neurodegenerative disease › inherited neurodegenerative disorder › Huntington disease and related disorders › Huntington disease-like syndrome › Machado-Joseph disease

Related subtypes (9): dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, Huntington disease-like 3, neuroferritinopathy, spinocerebellar ataxia type 17, neuroacanthocytosis, Huntington disease-like syndrome due to C9ORF72 expansions, childhood-onset benign chorea with striatal involvement

Subtypes (4): Machado-Joseph disease type 1, Machado-Joseph disease type 2, Machado-Joseph disease type 3, Machado-Joseph disease type 4

Genetics & variants

GWAS landscape

8 GWAS associations across 1 studies. Top hits map to 6 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs11529293	3e-06	IFTAP - RPL7AP56	T	2.71
rs11857349	3e-06	LRRC28, LINC02244	G	4.58
rs62171220	4e-06	THSD7B	G	2.71
rs7480166	4e-06	LINC02740 - HNRNPKP3	A	1.86
rs72660056	4e-06	ATP11A	A	3.29
rs8141510	4e-06	NFAM1	T	1.83
rs144891322	5e-06	RPS2P25 - PTP4A1P4	C	6.1
rs2067390	6e-06	INPP1	A	4.74

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST010248	Akcimen F	2020	700	0	Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	8

MAF distribution

Bucket	Variants
common (>=0.05)	6
low_freq (0.01-0.05)	2
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
intron_variant	6
intergenic_variant	2

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11529293	11	36833838	C>G,T	0.118	intron_variant	IFTAP - RPL7AP56	3e-06	Tier 4: intronic/intergenic
rs11857349	15	99384652	A>G,T	0.058	intron_variant	LRRC28, LINC02244	3e-06	Tier 4: intronic/intergenic
rs62171220	2	137045285	C>G,T	0.106	intron_variant	THSD7B	4e-06	Tier 4: intronic/intergenic
rs7480166	11	42963203	G>A,C,T	0.404	intergenic_variant	LINC02740 - HNRNPKP3	4e-06	Tier 4: intronic/intergenic
rs72660056	13	112853229	G>A,T	0.068	intron_variant	ATP11A	4e-06	Tier 4: intronic/intergenic
rs8141510	22	42425179	C>T	0.425	intron_variant	NFAM1	4e-06	Tier 4: intronic/intergenic
rs144891322	5	85839569	T>C	0.021	intergenic_variant	RPS2P25 - PTP4A1P4	5e-06	Tier 4: intronic/intergenic
rs2067390	2	190344302	T>A,G	0.038	intron_variant	INPP1	6e-06	Tier 4: intronic/intergenic

ClinVar germline variants

9 retrieved; paginated sample, class counts are floors:

3 benign, 2 uncertain significance, 1 pathogenic, 1 pathogenic; risk factor, 1 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
209995	NM_004993.5(ATXN3):c.886_888CAG(60_86) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN3	Pathogenic	no assertion criteria provided
3551	NM_004993.6(ATXN3):c.892CAG[8_36]	ATXN3	Pathogenic; risk factor	no assertion criteria provided
3780671	NM_004993.6(ATXN3):c.916_917insCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGC (p.Gly306fs)	ATXN3	Likely pathogenic	criteria provided, single submitter
402402	NM_004993.6(ATXN3):c.916_917insC (p.Gly306fs)	ATXN3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3780672	NM_004993.6(ATXN3):c.915_916insCAGCAGCAGCAGCAGCAGCAGCAGCAGCA (p.Gly306fs)	ATXN3	Uncertain significance	criteria provided, single submitter
3780673	NM_004993.6(ATXN3):c.891_892insGCAGCAGCAGCAG (p.Gln298fs)	ATXN3	Uncertain significance	criteria provided, single submitter
128515	NM_004993.6(ATXN3):c.916G>C (p.Gly306Arg)	ATXN3	Benign	criteria provided, single submitter
209994	NM_004993.5(ATXN3):c.886_888CAG(12_44) (p.Gln305_Gly306insGlnGlnGlnGlnGlnGlnGlnGlnGlnGlnGln)	ATXN3	Benign	no assertion criteria provided
931861	NM_004993.6(ATXN3):c.892CAG[12] (p.Gln302_Gln305dup)	ATXN3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ATXN3	Definitive	Autosomal dominant	Machado-Joseph disease	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATXN3	Orphanet:276238	Machado-Joseph disease type 1
ATXN3	Orphanet:276241	Machado-Joseph disease type 2
ATXN3	Orphanet:276244	Machado-Joseph disease type 3
ATP11A	Orphanet:2032	Idiopathic pulmonary fibrosis
ATP11A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	5
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATXN3	HGNC:7106	ENSG00000066427	P54252	Ataxin-3	gencc,clinvar
ATP11A	HGNC:13552	ENSG00000068650	P98196	Phospholipid-transporting ATPase IH	gwas
LRRC28	HGNC:28355	ENSG00000168904	Q86X40	Leucine-rich repeat-containing protein 28	gwas
THSD7B	HGNC:29348	ENSG00000144229	Q9C0I4	Thrombospondin type-1 domain-containing protein 7B	gwas
NFAM1	HGNC:29872	ENSG00000235568	Q8NET5	NFAT activation molecule 1	gwas
INPP1	HGNC:6071	ENSG00000151689	P49441	Inositol polyphosphate 1-phosphatase	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATXN3	Ataxin-3	Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates.
ATP11A	Phospholipid-transporting ATPase IH	Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of t…
NFAM1	NFAT activation molecule 1	May function in immune system as a receptor which activates via the calcineurin/NFAT-signaling pathway the downstream cytokine gene promoters.
INPP1	Inositol polyphosphate 1-phosphatase	Mg(2+)-dependent phosphatase that catalyzes the hydrolysis of the 1-position phosphate from inositol 1,4-bisphosphate and inositol 1,3,4-trisphosphate and participates in inositol phosphate metabolism.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 4 · Druggable fraction: 0.17

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Phosphatase	1	14.0×	0.208
Transcription factor	1	1.4×	0.539
Other/Unknown	4	1.2×	0.539

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATXN3	Other/Unknown	no		UIM_dom, Josephin, Ataxin-3
ATP11A	Transcription factor	no	7.6.2.1	P_typ_ATPase, P-type_ATPase_IV, ATPase_P-typ_transduc_dom_A_sf
LRRC28	Other/Unknown	no		Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf
THSD7B	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, TSP1_spondin_dom
NFAM1	Other/Unknown	no		Phos_immunorcpt_sig_ITAM, NFAM1, Ig_NFAM1
INPP1	Phosphatase	yes	3.1.3.57	Inositol_monophosphatase-like, Inositol_monophosphatase_CS, Inositol_monoP_metal-BS

Expression context

Cohort genes with no expression data: 0.

6 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	1
colonic epithelium	1
tendon	1
germinal epithelium of ovary	1
heart right ventricle	1
visceral pleura	1
ileal mucosa	1
left testis	1
right testis	1
cortical plate	1
male germ line stem cell (sensu Vertebrata) in testis	1
pigmented layer of retina	1
blood	1
leukocyte	1
monocyte	1
esophagus squamous epithelium	1
male germ cell	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATXN3	269	ubiquitous	marker	calcaneal tendon, colonic epithelium, tendon
ATP11A	268	ubiquitous	marker	germinal epithelium of ovary, visceral pleura, heart right ventricle
LRRC28	216	ubiquitous	marker	ileal mucosa, left testis, right testis
THSD7B	151	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, pigmented layer of retina, cortical plate
NFAM1	229	broad	marker	monocyte, leukocyte, blood
INPP1	293	ubiquitous	marker	sperm, male germ cell, esophagus squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATXN3	3,125
ATP11A	1,512
INPP1	1,183
NFAM1	901
THSD7B	756
LRRC28	674

Structural data

PDB: 1 · AlphaFold-only: 5 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATXN3	P54252	7

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LRRC28	Q86X40	90.30
INPP1	P49441	87.87
ATP11A	P98196	83.48
NFAM1	Q8NET5	72.19
THSD7B	Q9C0I4	67.23

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 25. Enrichment computed across 6 evidence-associated genes (5 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Josephin domain DUBs	1	190.3×	0.054	ATXN3
Synthesis of IP2, IP, and Ins in the cytosol	1	152.3×	0.054	INPP1
Inositol phosphate metabolism	1	95.2×	0.054	INPP1
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes	1	76.1×	0.054	ATXN3
FOXO-mediated transcription	1	67.2×	0.054	ATXN3
Defective B3GALTL causes PpS	1	61.7×	0.054	THSD7B
O-glycosylation of TSR domain-containing proteins	1	60.1×	0.054	THSD7B
Neutrophil degranulation	2	9.2×	0.054	ATP11A, NFAM1
Diseases associated with O-glycosylation of proteins	1	43.1×	0.055	THSD7B
Ion transport by P-type ATPases	1	41.5×	0.055	ATP11A
Post-translational protein modification	2	7.7×	0.055	ATXN3, THSD7B
O-linked glycosylation	1	28.9×	0.071	THSD7B
Diseases of glycosylation	1	26.2×	0.071	THSD7B
Deubiquitination	1	24.8×	0.071	ATXN3
Ion channel transport	1	19.2×	0.085	ATP11A
Metabolism of proteins	2	5.0×	0.086	ATXN3, THSD7B
Diseases of metabolism	1	16.1×	0.089	THSD7B
Innate Immune System	1	5.1×	0.242	ATP11A
Transport of small molecules	1	5.0×	0.242	ATP11A
RNA Polymerase II Transcription	1	4.5×	0.254	ATXN3
Gene expression (Transcription)	1	3.6×	0.298	ATXN3
Generic Transcription Pathway	1	3.0×	0.330	ATXN3
Disease	1	2.6×	0.344	THSD7B
Immune System	1	2.6×	0.344	ATP11A
Metabolism	1	2.3×	0.362	INPP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to cytosolic proteasome complex	1	2808.7×	0.013	ATXN3
regulation of cell-substrate adhesion	1	936.2×	0.018	ATXN3
regulation of membrane lipid distribution	1	468.1×	0.018	ATP11A
positive regulation of B cell receptor signaling pathway	1	401.2×	0.018	NFAM1
actin cytoskeleton organization	2	26.4×	0.018	ATXN3, THSD7B
monoubiquitinated protein deubiquitination	1	312.1×	0.018	ATXN3
positive regulation of myotube differentiation	1	255.3×	0.018	ATP11A
cellular response to misfolded protein	1	234.1×	0.018	ATXN3
regulation of B cell differentiation	1	216.1×	0.018	NFAM1
phosphate-containing compound metabolic process	1	165.2×	0.018	INPP1
intermediate filament cytoskeleton organization	1	156.0×	0.018	ATXN3
positive regulation of ERAD pathway	1	147.8×	0.018	ATXN3
calcineurin-NFAT signaling cascade	1	140.4×	0.018	NFAM1
protein quality control for misfolded or incompletely synthesized proteins	1	127.7×	0.018	ATXN3
exploration behavior	1	108.0×	0.018	ATXN3
protein K48-linked deubiquitination	1	108.0×	0.018	ATXN3
phospholipid translocation	1	104.0×	0.018	ATP11A
protein K63-linked deubiquitination	1	104.0×	0.018	ATXN3
intracellular signal transduction	2	12.7×	0.018	LRRC28, NFAM1
positive regulation of ubiquitin-dependent protein catabolic process	1	93.6×	0.019	ATXN3
phosphatidylinositol phosphate biosynthetic process	1	80.2×	0.021	INPP1
B cell receptor signaling pathway	1	66.9×	0.024	NFAM1
nucleotide-excision repair	1	63.8×	0.024	ATXN3
cellular response to heat	1	57.3×	0.026	ATXN3
negative regulation of TORC1 signaling	1	54.0×	0.026	ATXN3
cellular response to amino acid starvation	1	53.0×	0.026	ATXN3
positive regulation of cytokine production	1	45.3×	0.029	NFAM1
B cell differentiation	1	36.5×	0.035	NFAM1
protein deubiquitination	1	29.6×	0.041	ATXN3
microtubule cytoskeleton organization	1	20.2×	0.057	ATXN3

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Lithium Carbonate, Trehalose, Varenicline.

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 6

Druggability breadth: 1 of 6 evidence-associated genes (17%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATXN3	0	0
ATP11A	0	0
LRRC28	0	0
THSD7B	0	0
NFAM1	0	0
INPP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ATXN3	7	Binding:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATP11A	7.6.2.1	P-type phospholipid transporter
INPP1	3.1.3.57	inositol-1,4-bisphosphate 1-phosphatase

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	INPP1
E	Difficult family or no structure, no drug	5	ATXN3, ATP11A, LRRC28, THSD7B, NFAM1

Undrugged target profiles

6 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ATXN3	7	—
ATP11A	0	—
LRRC28	0	—
THSD7B	0	—
NFAM1	0	—
INPP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 30.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	18
PHASE2	6
PHASE2/PHASE3	2
PHASE3	2
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT01096082	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3
NCT05490563	PHASE2/PHASE3	TERMINATED	STRIDES - a Clinical Research Study of an Investigational New Drug to Treat Spinocerebellar Ataxia
NCT03378414	PHASE2	NOT_YET_RECRUITING	Umbilical Cord Mesenchymal Stem Cells Therapy (19#iSCLife®-SA) for Patients With Spinocerebellar Ataxia
NCT05822908	PHASE1/PHASE2	RECRUITING	A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD
NCT00992771	PHASE2	COMPLETED	Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3
NCT01096095	PHASE2	WITHDRAWN	Pilot Study of Safety and Efficacy of Sodium Phenylbutyrate in Spinocerebellar Ataxia Type 3
NCT02039206	PHASE2	COMPLETED	The Influence of Deep TMS on Cerebellar Signs in Patients With Machado Joseph Disease
NCT02147886	PHASE2	COMPLETED	Study To Assess Safety, Tolerability and Efficacy of Intravenous Cabaletta in Patients With Machado-Joseph Disease
NCT04301284	PHASE2	WITHDRAWN	Study of CAD-1883 for Spinocerebellar Ataxia
NCT05160558	PHASE1	TERMINATED	A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT05826171	Not specified	ACTIVE_NOT_RECRUITING	Priming Motor Learning Through Exercise in People With Spinocerebellar Ataxia
NCT01060371	Not specified	UNKNOWN	Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias
NCT02175290	Not specified	UNKNOWN	Machado-Joseph Disease in Israel
NCT02906046	Not specified	COMPLETED	Weight in Lower Limbs Improves Gait Ataxia of in Machado-Joseph Disease Patients
NCT03120013	Not specified	COMPLETED	Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia
NCT03487367	Not specified	UNKNOWN	Clinical Trial Readiness for SCA1 and SCA3
NCT03885167	Not specified	COMPLETED	Identification of Biomarkers in Spinocerebellar Ataxia 3
NCT04153110	Not specified	COMPLETED	Cerebello-Spinal tDCS as Rehabilitative Intervention in Neurodegenerative Ataxia
NCT04229823	Not specified	UNKNOWN	Natural History of Oculomotor Neurophysiology in Ataxic and Pre-ataxic Carriers of SCA3/MJD
NCT04268147	Not specified	COMPLETED	Instrumented Data Exchange for Ataxia Study
NCT04399265	Not specified	UNKNOWN	Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3
NCT04419974	Not specified	UNKNOWN	Astrocytic Markers and the Pre-ataxic Period of SCA3/MJD - BIGPRO Study Astrocytes
NCT04426149	Not specified	COMPLETED	Clinical Effects of Oral Trehalose In Patients With Spinocerebellar Ataxia 3
NCT04714307	Not specified	UNKNOWN	Neuropsychiatry and Cognition in SCA3/MJD
NCT05486806	Not specified	UNKNOWN	Longitudinal Tracking of Patients Diagnosed With Neurodegenerative Movement Disorders
NCT05502432	Not specified	COMPLETED	Repetitive Transcranial Magnetic Stimulation in SCA3 Patients
NCT05557786	Not specified	COMPLETED	Treatment of Transcranial Alternating Current Stimulation（tACS）on Cerebellar Ataxia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
PHENYLBUTANOIC ACID	4	2
LITHIUM CARBONATE	4	1
VARENICLINE	4	1
TRORILUZOLE	3	3
TREHALOSE	3	2
MALTOSE	3	1
RIMTUZALCAP	2	1