Details of Disease

General Information of Disease (ID: DISDL1IO)

Disease Name Alexander disease
Synonyms alexanders leukodystrophy; megalencephaly in infancy accompanied by progressive spasticity and dementia; ALXDRD; Alexander's disease; AxD; Alexander disease
Disease Class 8A44: Leukodystrophy
Definition
Alexander disease (AxD) is a rare neurodegenerative disorder of the astrocytes comprised of two clinical forms: AxD Type I and Type II manifesting with various degrees of macrocephaly, spasticity, ataxia and seizures and leading to psychomotor regression and death.
Disease Hierarchy
DISVY1TT: Leukodystrophy
DISDL1IO: Alexander disease
ICD Code
ICD-11
ICD-11: 8A44.2
Disease Identifiers
MONDO ID
MONDO_0008752
MESH ID
D038261
UMLS CUI
C0270726
OMIM ID
203450
MedGen ID
78724
Orphanet ID
58
SNOMED CT ID
81854007

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)
This Disease is Treated as An Indication in 1 Clinical Trial Drug(s)
Drug Name Drug ID Highest Status Drug Type REF
ION373 DMHI0KL Phase 3 Antisense oligonucleotide [1]
------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 4 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
CASP6 TTKW4ML Strong Altered Expression [2]
ITPR2 TTK9OV3 Strong Biomarker [3]
CRYAB TT7RUHB Definitive Biomarker [4]
GFAP TTI6FFX Definitive Autosomal dominant [5]
------------------------------------------------------------------------------------
This Disease Is Related to 3 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
DES OTI09KBW Limited Genetic Variation [6]
HSPB2 OTS01646 Limited Biomarker [4]
GFAP OTQ01ZAS Definitive Autosomal dominant [5]
------------------------------------------------------------------------------------

References

1 ClinicalTrials.gov (NCT04849741) A Phase 1-3, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Pharmacodynamics of Intrathecally Administered Zilganersen (ION373) in Patients With Alexander Disease. U.S.National Institutes of Health.
2 Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander disease severity.Elife. 2019 Nov 4;8:e47789. doi: 10.7554/eLife.47789.
3 Aberrant astrocyte Ca(2+) signals "AxCa signals" exacerbate pathological alterations in an Alexander disease model.Glia. 2018 May;66(5):1053-1067. doi: 10.1002/glia.23300. Epub 2018 Jan 31.
4 Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease.APMIS. 2014 Jan;122(1):76-80. doi: 10.1111/apm.12088. Epub 2013 Apr 18.
5 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
6 Disorders of Astrocytes: Alexander Disease as a Model.Annu Rev Pathol. 2017 Jan 24;12:131-152. doi: 10.1146/annurev-pathol-052016-100218.