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Gene therapy for intracranial aneurysms: systemic review
Malia McAvoy1, Buddy Ratner2, Manuel J Ferreira1
1Neurological Surgery, University of Washington, Seattle, Washington, USA.
Abstract:
Treatment of intracranial aneurysms is currently limited to invasive surgical and endovascular modalities, and some aneurysms are not treatable with these methods. Identification and targeting of specific molecular pathways involved in the pathogenesis of aneurysms may improve outcomes. Low frequency somatic variants found in cancer related genes have been linked to intracranial aneurysm development. In particular, mutations in the PDGFRB gene lead to constitutively activated ERK and nuclear factor κB signaling pathways, which can be targeted with tyrosine kinase inhibitors. In this review, we describe how low frequency somatic variants in oncogenic and other genes affect the pathogenesis of aneurysm development, with a focus on gene therapy applications, such as endovascular in situ delivery of chemotherapeutics.
Insights
Targeting cancer-related genes in intracranial aneurysms shows promise. Mutations in genes like PDGFRB activate pathways treatable with tyrosine kinase inhibitors and gene therapy.
Area of Science:
- Neuroscience
- Oncology
- Genetics
Background:
- Intracranial aneurysms pose treatment challenges, with some cases unresponsive to current surgical and endovascular methods.
- Low-frequency somatic variants in cancer-related genes are implicated in intracranial aneurysm development.
- Mutations in the PDGFRB gene activate ERK and NF-κB signaling, offering therapeutic targets.
Purpose of the Study:
- To review the role of low-frequency somatic variants in oncogenes and other genes in aneurysm pathogenesis.
- To explore gene therapy applications for intracranial aneurysms, focusing on endovascular delivery.
Main Methods:
- Literature review of studies on somatic variants and intracranial aneurysms.
- Analysis of molecular pathways, including ERK and NF-κB signaling.
- Discussion of targeted therapies like tyrosine kinase inhibitors and gene therapy.
Main Results:
- Somatic variants in cancer-related genes contribute to aneurysm formation.
- PDGFRB mutations exemplify how genetic alterations activate key signaling pathways.
- Tyrosine kinase inhibitors and gene therapy represent potential novel treatment strategies.
Conclusions:
- Targeting specific molecular pathways offers a promising avenue for treating intracranial aneurysms.
- Gene therapy, particularly endovascular in situ delivery, holds potential for difficult-to-treat aneurysms.
- Further research into somatic variants and targeted therapies could revolutionize aneurysm treatment.
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