Fibrin drives thromboinflammation and neuropathology in COVID-19 (copy)
Full author list: Ryu JK, Yan Z, Montano M, Sozmen EG, Dixit K, Suryawanshi RK, Matsui Y, Helmy E, Kaushal P, Makanani SK, Deerinck TJ, Meyer-Franke A, Rios Coronado PE, Trevino TN, Shin MG, Tognatta R, Liu Y, Schuck R, Le L, Miyajima H, Mendiola AS, Arun N, Guo B, Taha TY, Agrawal A, MacDonald E, Aries O, Yan A, Weaver O, Petersen MA, Meza Acevedo R, Alzamora MDPS, Thomas R, Traglia M, Kouznetsova VL, Tsigelny IF, Pico AR, Red-Horse K, Ellisman MH, Krogan NJ, Bouhaddou M, Ott M, Greene WC, Akassoglou K.
Preventing Brain Damage in Preterm Babies
“As a neonatologist and neuroscientist, it’s frustrating that we don’t have any treatments to counteract the harmful effects of bleeding in the developing brain, even though we know it often leads to lasting problems,” says Petersen, director of the Neuro-Intensive Care Nursery at UC San Francisco (UCSF), associate professor of pediatrics at UCSF, and a visiting scientist at Gladstone Institutes. “Adding to this frustration, we’ve had very little understanding — until now — of why and how this bleeding is so closely tied to the long-term neurological issues these babies often face.”
In a study that appears in Proceedings of the National Academy of Sciences (PNAS), Petersen and an interdisciplinary team of physicians and scientists from Gladstone and UCSF shed light on this vexing medical condition, showing for the first time that a blood protein called fibrin blocks an essential biological process that drives brain development in early life.
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Discovery of How Blood Clots Harm Brain and Body in COVID-19 Points to New Therapy
In a study that reshapes what we know about COVID-19 and its most perplexing symptoms, scientists have discovered that the blood coagulation protein fibrin causes the unusual clotting and inflammation that have become hallmarks of the disease, while also suppressing the body’s ability to clear the virus. Importantly, the team also identified a new antibody therapy to combat all of these deleterious effects.
Published in Nature, the study by Gladstone Institutes and collaborators overturns the prevailing theory that blood clotting is merely a consequence of inflammation in COVID-19. Through experiments in the lab and with mice, the researchers show that blood clotting is instead a primary effect, driving other problems—including toxic inflammation, impaired viral clearance, and neurological symptoms prevalent in those with COVID-19 and long COVID.
“Knowing that fibrin is the instigator of inflammation and neurological symptoms, we can build a new path forward for treating the disease at the root,” says Katerina Akassoglou, PhD, a senior investigator at Gladstone and the director of the Center for Neurovascular Brain Immunology at Gladstone and UC San Francisco. “In our experiments in mice, neutralizing blood toxicity with fibrin antibody therapy can protect the brain and body after COVID infection.”
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