As the clock strikes the 18th minute, a terrifying bomb detonates within someone’s head. However, these are not your typical bombs. Known as brain aneurysms, nearly 6.5 million Americans have one of these volatile explosives slowly counting down to zero, with around 30,000 of them annually experiencing ruptures that lead to brain bleeding. Though these explosions of blood may not spell certain death, nearly half of all affected victims are fatally injured and approximately two-thirds of survivors suffer from permanent neurological deficits [1].
With these high mortality and morbidity rates, many treatments have emerged to prevent and counter the deadly effects of brain aneurysm ruptures. Following the first open surgery for brain aneurysms performed in 1938, surgical clipping was regarded as the only definitive treatment for aneurysms for the majority of the 20th century [2]. Marked by the removal of a skull section and the manual placement of a metal clip at the aneurysm neck, surgical clipping often resulted in extensive, difficult postoperative recoveries [3].
However, with the shift in recent decades towards minimally invasive treatments, endovascular coiling emerged as the most prominent procedure for ruptured aneurysms following its invention in the 1990s. Through the insertion of a catheter to the brain aneurysm site, thin platinum coils are subsequently deployed within the aneurysm sac to isolate it from the main blood flow, effectively eliminating the threat of rupture [4]. Though endovascular coiling produces successful outcomes in nearly 70-80% of treated cases, success rates can be substantially lower depending on aneurysm location and geometry. In particular, after coiling with standard platinum coils, aneurysms can reoccur at rates of 5-20% in small aneurysms, 35-50% in large aneurysms, and 60-90% in giant aneurysms [5]. Additionally, complications ranging from brain swelling, fluid buildup, hematomas, and more can result from the permanent, metallic nature of the coils [6].
As such, what is the best method to go about curing these aneurysms before the clock runs out? With the urgent need to develop improved procedures, one innovative therapy represents an exciting avenue for the future of brain aneurysm treatments: liquid embolic agents (LEAs).
LEAs are polymer-based aqueous solutions that are injected as liquids through catheters and deposited at the aneurysm site as durable, gelatinous solids. With advantages over existing therapies including ease, short procedure times, immediate isolation from the primary blood vessel, and efficacy for aneurysms with complex morphologies, LEAs are able to fully occlude aneurysms of most configurations with high success [7].
The GPX Embolic Device is one such LEA currently under development by Fluidx Medical Technology that holds significant potential for brain aneurysm treatments. Harnessing a “concentrated polyelectrolyte solution that is produced using a blend of oppositely charged polymers,” the GPX consists of sodium and chloride counterions that allow for its delivery in a fluid state and its subsequent solidification “in response to the lower concentration of monovalent ions in the blood” [8]. A study conducted by Fries et al. investigated the efficacy of the GPX in terms of occlusion rate and tissue response through the use of rabbit aneurysm models. They discovered that not only all aneurysms in their experiments were entirely occluded by the GPX without any traces of blood clotting, leakage, tissue death, or recurrence, but also that endothelial tissue repair occurred along the aneurysm neck [8]. Though the rabbits were only assessed in the short term for one month, these preliminary positive outcomes provide hope for a future without brain aneurysm reappearances, complications, or ruptures.
Despite the GPX Embolic Device still having a lengthy road to go before approval and commercialization, its promising results pave the way for emerging LEAs to dominate the brain aneurysm treatment market in the future. But as we wait until that day comes, we know for certain that it is truly possible to defuse these ticking time bombs before it is too late.
References
- Statistics and Facts. Brain Aneurysm Foundation. (2021, May). http://www.bafound.org/about-brain-aneurysms/brain-aneurysm-basics/brain-aneurysm-statistics-and-facts/.
- Maurice-Williams, R. S., & Lafuente, J. (2003, November). Intracranial Aneurysm Surgery and its Future. Journal of the Royal Society of Medicine. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539625/.
- Krans, B. (2017, July 9). Brain aneurysm repair: Procedure, preparation, and risks. Healthline. https://www.healthline.com/health/brain-aneurysm-repair.
- Mayfield Brain & Spine. (n.d.). Aneurysm Embolization: Coiling, Stenting, Flow Diversion. Aneurysm Coiling, Stenting & Flow Diversion | Mayfield Brain & Spine Cincinnati, OH. http://www.mayfieldclinic.com/pe-coiling.htm.
- Marbacher, S., Niemela, M., Hernesniemi, J., & Frosen, J. (2019, March). Recurrence of endovascularly and microsurgically treated intracranial aneurysms-review of the putative role of aneurysm wall biology. Neurosurgical review. https://pubmed.ncbi.nlm.nih.gov/28819834/.
- Fanning, N. F., Willinsky, R. A., & Brugge, K. (2008, June). Wall enhancement, edema, and hydrocephalus after endovascular coil occlusion of intradural cerebral aneurysms. Journal of Neurosurgery. https://pubmed.ncbi.nlm.nih.gov/18518706/.
- Takao, H., Murayama, Y., Saguchi, T., Ishibashi, T., Ebara, M., Irie, K., Yoshioka, H., Mori, Y., Ohtsubo, S., Viñuela, F., & Abe, T. (2006, January 20). Endovascular treatment of experimental cerebral aneurysms using thermoreversible liquid embolic agents. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387944/.
- Fries, F., Tomori, T., Schulz-Schaeffer, W. J., Jones, J., Yilmaz, U., Kettner, M., Simgen, A., Reith, W., & Mühl-Benninghaus, R. (2021, May 4). Treatment of experimental aneurysms with a gpx embolic agent prototype: Preliminary angiographic and histological results. Journal of NeuroInterventional Surgery. https://jnis.bmj.com/content/early/2021/06/29/neurintsurg-2021-017308.