Gene Therapy and Endovascular Treatment of Intracranial Aneurysms

Abstract

Background-Endovascular treatment of intracranial aneurysms is safe and effective but too often is followed by recurrences. Gene therapy may improve healing after embolization, and endovascular approaches may offer future in situ delivery systems designed to prevent aneurysm rupture. Summary of Review-Advances in coil technology have focused on coating strategies designed to modify the biological reaction to the embolic agent. Gene therapy in cardiovascular applications is limited by low efficiency and transient gene expression. Current advances include the potential use of circulating progenitor cells for ex vivo genetic manipulations followed by in vivo delivery. Direct gene transfer may also be enhanced in situ by coils carrying antibody-tethered adenovirus or through the use of cell-specific or radiation-inducible promoters. Candidate genes that may be of value in promoting healing after endovascular treatment include growth factors and metalloproteinase inhibitors. A better understanding of the biology of aneurysm is necessary to conceive strategies designed to control the development of these lesions before their rupture. Conclusions-Many

Endovascular Treatment of Experimental Aneurysms by Use of Fibroblast-Coated Platinum Coils

“…Although fibroblasts are a promising cell type, difficulty in harvest may limit widespread application. We anticipate, as have other groups, 32 that circulating progenitor cells may represent the ideal candidate cell for treatment of aneurysms. These progenitor cells are easily harvested and expanded ex vivo.…”

Review of Cerebral Aneurysm Formation, Growth, and Rupture

“…Gene therapy, a technique that consists of inserting a functioning gene into a cell to correct a genetic error or to introduce a new function may be a potential therapeutic strategy for CAs. 57 For example, gene therapy for inhibiting the overexpression of MMPs, the activation of macrophages, or the phenotypic modulation of SMCs may theoretically have efficacy in preventing aneurysm rupture. Unfortunately, however, gene therapies have the best chance of success only if a specific defective gene is identified, as in cystic fibrosis, for example.…”

“…Promoting healing after coil embolization is another application of gene therapy, and coils carrying antibody-tethered adenovirus may enhance direct gene transfer. 57 Candidate genes are those involved in vascular remodeling and include growth factors, metalloproteinase inhibitors, and MCP-1.…”

A Modified Technique Improved Histology Similarity to Human Intracranial Aneurysm in Rabbit Aneurysm Model

“…The overall risk of rupture found in follow-up studies is around 1% per year 1 . For unruptured intracranial aneurysms, both clipping and coiling treatment modalities have a risk of around 6% of complications leading to death or disability for aneurysms smaller than 10 mm, these rates often equaled or exceeded the natural rupture risk 2 , so there is growing interest in targeted aneurysm wall repair for unruptured aneurysms 3,4 . It is well established that aneurysm formation and development is a gradual process of degeneration of extracellular matrix (ECM) and loss of the cellular component.…”