When you think of Dr. Dalton Dietrich, you should think of inflammasomes. His research group was the first to show inflammasome signaling in brain cells, neurons, microglia, astrocytes, and other things of this nature. However, most people have never heard of inflammasomes or how critical they may be to the research and treatment of traumatic brain injury (TBI). I sat down with Dr. Dietrich recently to discuss the latest developments in his research.
What are inflammasomes?
Inflammasomes are a multi-protein complex of the innate immune response. This immune response happens immediately when a cell is stressed and is responsible for controlling our body’s inflammatory response. Inflammasomes are a regulator that occurs through the activation of the inflammatory caspase known as Caspase-1, typically in response to viruses, bacteria, and other sources of stress to the cell. The activation of Caspase-1 leads to the formation of the pro-inflammatory cytokines IL-1 beta and IL-118, as well as gasdermin activation, which forms gaps in cells that kill them through a process called pyroptosis. Dr. Dietrich notes that inflammasomes are also extremely relevant at the moment because they play a role in the body’s response to COVID-19.
An upstream solution
With this information, Dr. Dietrich and his team developed a series of monoclonal antibodies that actually target the formation of inflammasomes. The antibodies prevent them from forming this complex and dramatically decrease the formation of IL-1 beta. It’s an “upstream” approach that intervenes in the very early stages of the inflammatory cascade that happens when a cell is stressed. Dietrich’s team has seen successful animal trials where the antibodies successfully blocked the inflammasomes and improved cognitive function. Hopefully human trials are just around the corner.
The other benefit to inflammasome research is how it can be used diagnostically. Inflammasome levels can be used to detect the severity of injury and the progression of pro-inflammatory mediators that could be associated with more progressive neurodegenerative diseases. Dietrich and his team use blood samples from TBI patients to measure the amount of inflammasomes in the bloodstream and identify potential biomarkers. I’m excited to see how inflammasome protein biomarkers further illuminate treatment solutions for TBI patients in the future!