A new path is emerging to both “identify and destroy the blood clots responsible for strokes”, according to Inserm researcher Thomas Bonnard and his team, based in Caen.
This 37-year-old researcher, with two colleagues from the BB@C laboratory (Blood and Brain at Caen-Normandie Editor's note), synthesized particles called PHySIOMIC to identify and destroy the tiny blood clots responsible for strokes, with more precision and less toxicity for the body than the current process.
Effective in mice, PHySIOMIC still needs to be tested on two “big animals”then the human being, and define a procedure to mass produce it before marketing it, which will not happen before “five to ten years”according to Thomas Bonnard.
“An ischemic stroke is caused by a clot which will migrate from the carotid artery and block the blood circulation in the brain, thus killing neurons. Today, we know how to see large clots on MRI (imaging by magnetic resonance Editor's note)” retrace M. Bonnard, “on the other hand, we did not know how to detect the smallest clots, or “microthrombi”.
The PHySIOMIC contrast agent is made up of microparticles of iron oxide and polydopamine: an assembly of molecules of the neurotransmitter dopamine by which neurons usually communicate, used here as a material. Once injected into the bloodstream, it will attach to the microclot and will be visible on MRI thanks to its magnetic properties.
There is “concerns” with the contrast agents currently used based on Gadolinium, “associated in the past with certain risks of renal complications”according to Thomas Bonnard. This is not the case, according to the researcher, of PHySIOMIC: “it will never have toxic effects, since it exclusively uses materials that are already present in the body.”
Like a mussel to its rock
The “MIC” of PHySIOMIC means “Mussel Inspired Clusters” (agglomerate inspired by mussels, in English) because the mussel, to attach itself to its rock, also uses dopamine. “When you inject something into the blood, proteins come” s’agglutiner “on it and participate in the attachment to the microclot”describes Charlène Jacqmarcq, 30 years old.
This post-doctoral student at BB@C is sitting in front of a “microfluidic post office” : a network of tubes and pumps responsible for reproducing the blood system in which it “simulate strokes” on human blood recovered in partnership with the French Blood Establishment (EFS).
Once identified, the microthrombi must be destroyed, research carried out by Audrey Picot, a 27-year-old doctoral student at the BB@C laboratory, who adds a tissue plasminogen activator (tPA) to PHySIOMIC. The only pharmacological treatment currently provided to stroke victims, tPA presents a risk of bleeding which will be reduced by targeting the contrast agent PHySIOMIC, according to Mr. Bonnard.
“We have set up a collaboration with the Australian pharmaceutical company CSL Behring, as well as Inserm Transfert, to develop this diagnostic tool and make it become a theranostic tool: this means that it will both diagnose and make visible microclots, allow their degradation and restore blood flow in patients”specifies Ms. Picot.
Paid by Inserm from the private funds of CSL Behring, the entire team benefits from the tools of the BB@C laboratory.
IRM “small animal”magnetic particle imaging scanner (the 1st in France), a super resolution 3D ultrasound machine… “We don’t find this material concentrated in one place in all the research centers, we are lucky to work here”rejoices Charlène Jacqmarcq.
“BB@C was founded by Inserm, the University of Caen and the Caen University Hospital” explains Denis Vivien, 58, professor of cell biology and director of the institute, “170 people work there associated with four startups to develop new therapeutic and diagnostic strategies, mainly on stroke”details its founder.
