Traumatic brain injury (TBI) affects 50 million people annually around the world. Individuals surviving moderate-to-severe TBI can develop complications that lead to long-term conditions, including neuroendocrine dysfunction, epilepsy, and other cognitive, behavioral, mental, or functional deficits. There are currently neither definitive neuroprotective treatments for TBI nor any biologic agents used to facilitate neural repair or recovery after TBI, but research has indicated that inflammation, including autoimmune responses, is a key mediator in complications following TBI. Longitudinal assessments of inflammatory markers paired with autoantibodies (AAbs), which circulate in serum up to one year post-injury, are yielding new insights on immunotherapy treatment methodologies to support the adaptive immune response and modulate innate and cellular immune responses in central nervous system (CNS) repair and neuroendocrine recovery post-TBI. This work points to novel therapeutic targets that may have broad implications for tissue repair in the urgent quest to promote neuroprotection and facilitate tissue repair after TBI and other forms of acquired brain injury.
Description
After CNS injuries, lymphopenia and neutrophilia occur in many individuals as part of an injury-induced and dysfunctional cellular immune response. Individuals with better outcomes after such injuries have significantly higher IL-7 protein production. IL-7 increases and enhances lymphoproliferation and facilitates the development of AAbs that promote neural repair in a response characterized as “protective autoimmunity” over at least the first six months post-injury. Recombinant humanized IL-7 (rhIL-7) may be a potential treatment target to amplify the lymphoproliferative response after TBI, leading to more complete recovery and lowering the risk of complications. Related work suggests elevated TNFR1 levels after TBI may mitigate the beneficial properties of IL-7, suggesting that TNFR1 inhibitors may be a useful co-treatment for some who may benefit from adaptive immunity boosting with rhIL-7. RhIL-7 has been shown to ameliorate age-related immunodeficiency, progressing leukocyte encephalopathy, some cancers, and sepsis, making it a promising biological target to consider for TBI. RhIL-7 function in these modalities support its potential utility and tolerability as a modifiable, rehabilitation-relevant, biological target to promote adaptive immunity and neuroendocrine function while mitigating risk of epilepsy and promoting neurorecovery when used with a TNFR inhibitor following TBI.
Applications
· Neuroprotection and tissue repair following traumatic brain injury
· Enhancing IGM-associated autoimmune response after TBI
· Increasing AAb production in patients who, due to aging, stress, sepsis, lymphopenia, or genetic variation, produce insufficient amounts
Advantages
· No other biologic agents for neural repair, recovery, or neuroprotection are currently in use
· IL-7 has been used successfully in small treatment trials to treat other diseases and disorders and is well-tolerated by patients
· TNFR inhibitors are well-tolerated and FDA approved for other diseases
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US20210196797A1
