Blood protein may reduce brain damage after stroke
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If you have a stroke, FSAP protein can help reduce the extent of paralysis and speech problems.
Each year, approximately 12 million people suffer from a stroke worldwide. A stroke happens suddenly and is caused by either a blood clot or a brain hemorrhage.
“Those who survive often suffer life-altering brain damage. In addition to the cost in human suffering, the care of these patients is very expensive for health systems. It is therefore important that we find treatments that can be applied immediately after a stroke. For every minute lost, more of the brain is damaged,” says Professor Sandip Kanse.
He is researching a protein called FSAP at the University of Oslo‘s Institute for Basic Medical Studies (UiO).
Scientists had already discovered that the amount of FSAP in the blood of patients increases after a stroke. Some people have a genetic mutation that causes them to have lower FSAPs, which puts them at a higher risk of having a stroke.
“Therefore, in theory, FSAP is beneficial for stroke patients. So we wanted to find out if FSAP could be used as a treatment for stroke,” says Kanse.
Mice treated with FSAP after stroke suffered less brain damage
Kanse and his team conducted experiments in mice in which they removed the gene responsible for producing FSAP in some mice.
A stroke was then induced in the mice.
“Mice with the FSAP gene removed suffered more brain damage than normal mice. This shows that the FSAP gene is important for brain protection. We then tested what would happen if we treated the mice with the FSAP protein after a stroke. Our results show that their condition has improved significantly,” says Kanse.
Simultaneous processing with TPA and FSAP
The next step was to administer FSAP to the mice along with the standard drug TPA. The researchers wanted to know if FSAP could improve the effect of TPA treatment.
The results were promising and show that the treatment combining TPA and FSAP had a better effect than TPA alone. This study has just been published in the FASEB Review.
TPA only works in a third of stroke patients
TPA has several flaws, it can dissolve blood clots in the brain, but it only works in a third of all patients.
TPA must also be given within 4.5 hours of the stroke – after this time it can damage the brain.
In 10% of patients, TPA causes severe bleeding in the brain.
“In other words, only 30% of stroke patients get better when given TPA. The alternative to this treatment is surgery, which requires instruments that can look into the brain and remove the blood clot via a catheter. Not all hospitals have such equipment, so it is not always possible to perform this type of surgery. Therefore, it is necessary to find other ways to treat strokes, ” says Professor Kanse.
Diagnosis and treatment must begin in the ambulance
UiO scientists have also developed an agent that can stimulate the body to produce more active FSAPs. It is easier to develop such an agent than to produce PASF itself.
An article on this research project was recently published in ACS Chim Biol.
“We now need more research to know whether or not triggering active FSAP production will work as a treatment for stroke. Ideally, diagnosis and treatment should start immediately in the ambulance itself,” says Kanse.
Reference:
Berge Seidl et al. Identification of a phage-display-derived peptide interacting with the N-terminal region of factor VII activating protease (FSAP) allows characterization of zymogen activation, ACS Chem. organic, 2022. DOI: 10.1021/acschembio.2c00538