A suite of neuroprotective monoclonal antibodies targeting CD11d, which has a role in inflammation
Traumatic injuries to the brain and spinal cord are a leading cause of death among young people. Patients who are fortunate to survive the initial injury often deal with lifelong neurological impairment. With incident rates on the rise, traumatic brain injury (TBI) and spinal cord (SCI) are poised to become a major contributor to the global epidemiological and economic burden among traumatic injuries.
The extent of the tissue damage suffered by TBI and SCI patients is determined not only by the primary injury sustained through mechanical forces applied to the tissues but through a secondary injury that occurs following the initial trauma. This secondary injury is the result of a complicated sequence of events initiated by the release of neurotoxic and endogenous inflammatory mediators by resident cells of the central nervous system. In SCI, secondary tissue damage and lesion expansion involve inflammatory events such as ischemia, oxidative damage, inflammatory cell infiltration and necrotic and apoptotic cell death. In TBI, microglia and astrocytes can produce pro-inflammatory cytokines and chemokines, together with the infiltrated leukocytes through the damaged bloodbrain barrier. Despite different pathologies, an immunomodulatory therapeutic targeted at reducing the negative aspects of neuroinflammation may produce comparable efficacy in minimizing the extent of the secondary injury following the initial insult in TBI and SCI patients, along with related indications such as systemic inflammatory response syndrome (SIRS).
There is a significant unmet need to develop therapeutics for SCI and TBI in both the civilian and military populations. Many programs have shown promising results in pre-clinical trials but all have failed in humans. Accordingly, there is ongoing desire to develop new therapeutic approaches to treat TBI and SCI.
Robarts Research Institute researchers at Western University have developed a suite of neuroprotective monoclonal antibodies targeting CD11d which plays a role in immune and inflammatory responses. CD11d is an important component of the CD11d/CD18 integrin expressed on the majority of circulating human neutrophils and monocytes/macrophages, NK, B and γδ T cells but not on αβT cells. Early treatment in animal (rat and mouse) models of SCI, TBI and SIRS prevents neuroinflammatory damage by neutrophils and macrophages resulting in improved neurological recovery. It is believed that these antibodies target CD11d expressed on the first wave of pro-inflammatory cells entering the wound site whereby neutrophil and macrophage accumulation is reduced, overall secondary injury-associated cell death is decreased and more neuronal tissue is spared further injury leading to better functional recovery.
Dekaban’s expertise is in developing immunotherapeutics that prevent or modify disease outcomes. His most recent efforts focused on characterizing the cellular inflammatory response to spinal cord injury and developing an antibody-based therapy to block leukocyte infiltration into the injured spinal cord. His research will contribute to a better understanding of the natural history of brain injury.
Improved Postnatal Gas Exchange in Newborn Infants with Severe Form of Respiratory Failure
Lungs perform gas exchange for the human body. In preterm infants, this lung function is impaired, and respiratory distress syndrome (RDS) is the major cause of mortality in neonates (newborn infants under 4 weeks old). Typical clinical routine utilizes mechanical ventilation to support the lungs in oxygenating blood or ECMO (extracorporeal membrane oxygenation) for gas exchange. However, in preterm and term neonates, both strategies are associated with complications. Mechanical ventilation damages the thin lining of the lung and under critically ill conditions (RDS, sepsis, and pneumonia), is insufficient to prevent death or long-term impairment. Currently, ECMO is invasive and requires surgery to connect the device directly to the central blood vessels and high priming volume, needing external blood addition and pump.
The present invention provides the world’s first passive lung assist device that is designed to be pumped by the baby’s heart and capable of gas exchange in ambient air; a concept termed as the artificial placenta. This novel artificial oxygenation device is pumpless, easy-to-use and miniaturized for neonates (to minimize the risk of excessive blood loss). The device can be connected to the umbilical vessels, is biocompatible and minimizes damage to blood cells. The device has been demonstrated in animal trials and is capable of supporting the needs of a 1-2 kg neonate and increase blood oxygen saturation from 70 – 100%.
Fusch is a Pediatric Neonatologist and chief physician of the clinic for newborns, children and adolescents at the Nuremberg Clinic. Previously, he was a Professor in Pediatrics at McMaster University. He has more than 15 years of extensive experience in improving short- and long-term outcomes of premature infants and high-risk term neonates which has resulted in more than 100 publications. Over the past ten years, he has been developing of a microfluidic artificial placenta, dual ex-vivo closed-loop placenta perfusion, and optimizing nutrition and growth of very low birth weight (VLBW) infants.
Selvaganapathy is a Professor in Mechanical Engineering and Canada Research Chair in Biomicrofluidics. He has over 20 years of experience in microfabrication and microfluidics. His research interests are in the development of microfluidic devices for drug discovery, drug delivery, diagnostics and artificial organs. He has more than ~80 publications, in the top journals in the field. Three of his inventions have been commercialized.
In addition, the team consists of Dr. John Brash, Dr. Niels Rochow (Pediatric Neonatologist), Dr. Gehard Fusch (Analytical Chemist), MohammedHussein Dabaghi (Microfabrication/microfluidics Engineer), Shelley Monkman (Animal Experiment Specialist).
A process of layering or additive manufacturing that builds a component from thin layers by heating and extruding thermoplastic filament.
Urbanic has been involved with design, implementation, and support for several types of manufacturing, material handling, testing, gauging and assembly equipment for a variety of engine components and vehicle styles. She is an Associate Professor in the Department of Mechanical, Automotive, and Materials Engineering at UWindsor, and teaches courses related to design and technical communication, such as systems design, computer aided design and manufacturing, and senior design projects.