Study
An alternative splicing modulator decreases mutant HTT and improves the molecular fingerprint in Huntington’s disease patient neurons
| Study ID | Alternative Stable ID | Type |
|---|---|---|
| EGAS00001006289 | Other |
Study Description
Huntington's disease (HD) is a neurodegenerative disorder caused by poly-Q expansion in the Huntingtin (HTT) protein. Here, we delineate elevated mutant HTT (mHTT) levels in patient-derived cells including fibroblasts and iPSC derived cortical neurons using a GLP approved HTT assay. HD patients’ fibroblasts and cortical neurons recapitulate aberrant alternative splicing as a molecular fingerprint of HD. Branaplam is a splicing modulator currently tested in a phase II study in HD (NCT05111249). The drug lowers total HTT (tHTT) and mHTT levels in fibroblasts, iPSC, cortical progenitors, and neurons in a dose dependent manner at an IC50 consistently below 10nm without inducing cellular toxicity. Branaplam promotes inclusion of non-annotated novel exons. Amongst, a 115bp frameshift-inducing exon in the HTT transcript in Branaplam treated cells from Ctrl and HD patients leading to a profound reduction of HTT RNA and protein levels. Importantly, Branaplam ameliorates aberrant alternative splicing in HD patients’ fibroblasts and cortical neurons. These findings highlight the ... (Show More)
Study Datasets 2 datasets.
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
| Dataset ID | Description | Technology | Samples |
|---|---|---|---|
| EGAD00001008807 |
n=4 Ctrl and n=4 HD fibroblasts lines were treated with DMSO or 10nM Branaplam for 72h and RNA-seq was performed.
|
Illumina NovaSeq 6000 | 16 |
| EGAD00001008808 |
n=3 Ctrl and n=3 HD iPSC lines differentiated into cortical neurons were treated with DMSO or 10nM Branaplam for 72h and RNA-seq was performed.
|
Illumina NovaSeq 6000 | 12 |
Who archives the data?
Publications
Citations
Retrieving...
Retrieving...
