2023-06-28 14:20:00
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Aneurysms are balloon-like inflated blood vessels that can rupture suddenly and lead to death. Even if they are discovered early, there are hardly any therapies. A Japanese researcher wants to change that.
For those affected, it is a ticking time bomb, this balloon-like inflated blood vessel in the head. Hirofumi Nakatomi knows his patients’ fears. The brain surgeon at the renowned Riken Research Institute in Japan operates on many people with aneurysms – bulges in cerebral arteries that are usually discovered by accident and, depending on their size, can burst.
The procedure is tricky because the aneurysm could also rupture. “My patients want nothing more than a gentler, less risky therapy,” says the neurosurgeon. For example with a drug.
Often, but mostly unnoticed
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In Switzerland, over 3 percent of adults and thus over 250,000 people have one or more aneurysms in the brain, often without feeling anything. However, depending on its location or size, the aneurysm can rupture and cause cerebral hemorrhage. Smoking or high blood pressure increase this risk. Most of the time, the abnormality is discovered incidentally when a CT or MRI scan of the head is done for some reason. Whether the aneurysm is then removed or not is often a dilemma for physicians: Do you want to operate on an apparently healthy patient as a preventive measure – or do you accept the risk of the vessel rupturing?
The aneurysm is surgically clamped off with a tiny clamp called a clip. There is also the option of filling the bulge with a “coil” – a tiny platinum spiral – with the help of a catheter that is inserted into the artery through a small incision. Both procedures carry some risk of the aneurysm rupturing.
A team led by Hirofumi Nakatomi has approached this goal. They have discovered that the aneurysms are most likely caused by local gene mutations in the blood vessels, such as those found in a Study in the journal Science Translational Medicine write.
They owe this insight to the groundbreaking technology of Next Generation Sequencing, says Nakatomi. He and his team had taken 65 aneurysm tissue samples during operations and sequenced the entire exome from the cells in the samples; Exomes are the sections of DNA that are responsible for making a specific protein. In the analysis, the researchers found mutations in 16 genes. For comparison, they also sequenced the exomes of healthy blood vessels in the brain – the mutations only occurred in the aneurysm samples.
They also discovered that some of these genes control – or miscontrol – a common biological signaling pathway that is central to stable blood vessels, the so-called NF-kappa B signaling pathway. In the next step, the researchers blocked this dysregulated signal in a mouse model. With success.
Yvonne Doering is Head of Research for Vascular Diseases at the Inselspital and the University of Bern. Doering is impressed by the study by the Japanese research colleagues: “They introduced a central gene from their analysis and its mutated variant into the mouse, after which the mouse developed an aneurysm-like structure in its brain – twice the size of the original artery.”
Next, the researchers looked for a drug to block the mutated gene. According to Yvonne Doering, they also succeeded: “The experiment showed that it would be possible to treat a brain aneurysm with medication instead of resorting to a knife.”
How realistic is that for everyday clinical practice? David Bervini is a neurosurgeon at Inselspital Bern and specializes in aneurysm surgery. The work of the Japanese colleagues convinced him too: “This study is very hopeful and opens the door to a possible future therapy.”
An aneurysm in itself is not always dangerous, but living with the risk that it could rupture is very stressful for patients. “A drug could actually help here,” says David Bervini.
Hirofumi Nakatomi from the Japanese Riken Institute is already planning the next step: he wants to start a clinical study and is currently looking for partners from the pharmaceutical industry. So he hopes to find the best possible drug. Even if, as he jokes, it costs him his job as a neurosurgeon.
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