Omics · study · 2026
Thalidomide Reverses Sporadic Arteriovenous Malformation in the Central Nervous System
Listed in NCBI GEO
Sporadic arteriovenous malformations of the central nervous system (CNS-AVMs) are caused by somatic activating mutations of KRAS within endothelial cells (ECs) of the brain and spinal cord.
Description
There is no approved drug for this disease because the lack of a clinically representative animal model has hindered drug discovery. Here, we developed a novel mouse model of sporadic brain AVM (BAVM) induced by intracerebral injection of AAV-BR1-KRASG12V.
This model faithfully recapitulates the clinical manifestations, radiology, pathology, and transcriptomic profiles of human sporadic BAVM. Connectivity Map database analysis revealed thalidomide as a promising therapeutic. Preclinical experiments revealed that thalidomide can restore mural cell coverage with downregulating Angiopoietin 2 (ANGPT2) in ECs and inhibiting BAVM progression.
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This effect reduced hemorrhage and prolonged the survival of mice with BAVM. We then administered thalidomide to 30 patients with sporadic CNS-AVMs. Over a median treatment duration of 7.3 months, AVM lesions regressed in 60.7% of patients, while symptoms improved in 10.7%.
Biopsies demonstrated that thalidomide increased mural cell coverage and decreased ANGPT2 expression in ECs within AVM lesions. In summary, we established a representative model of sporadic BAVM and provided promising evidence supporting the therapeutic potential of thalidomide for sporadic CNS-AVMs.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE305nnn/GSE305291 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE305291 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1305002 ncbi.nlm.nih.gov/bioproject/PRJNA1305002 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Disease 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE305291 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |