There is increasing recognition that elevated levels of inflammatory mediators such as the principal mediator Tumor Necrosis Factor (TNF), an immune signaling molecule that we have demonstrated is also a neuromodulator, not only is required for normal biological functions in the brain, but in excess interferes with functional connectivity. Our research to date documents the rapid and sustained neurological improvements that ensue after perispinal administration of a single dose of a TNF blocking agent that rapidly neutralizes excess TNF, reduces microglial activation, and modulates synaptic and brain network function. Large molecule anti-TNF agents, when given systemically, are mostly excluded from the brain. Thus, a minimally invasive, perispinal (venous plexus surrounding spine) peripheral injection will be used for effective delivery of TNF blocking drugs to the brain. The success of this approach, paired with limited knowledge of brain TNF signaling, compels us to decipher the role of TNF in the brain ventricles, its TNF receptors, down-stream brain signaling molecules, and blood-brain/cerebrospinal fluid (CSF) barrier mechanisms involved in a plethora of brain pathologies. The founding research team has conducted pioneering research detailing the role of TNF in brain function. This research has been and promises to continue to be of significant value with regard to the understanding of the role of TNF in the modulation of brain function.
Expansion of this research going forward is exciting for the following reasons. By selectively targeting the brain non-invasively with anti-TNF compounds, practitioners can reduce and ameliorate an inflammatory response within the brain subsequent to trauma both in the periphery as well as in the brain. We do know that excess or prolonged inflammation can cause damage to tissues, but in particular the brain parenchyma. The administration of anti-TNF drugs directed solely to the brain can reduce or arrest the inflammatory response. Certainly, achieving reduced inflammation in the brain after succumbing to an insult can reverse damage. These favorable brain effects are consistent with improvements in brain functional connectivity.
This work has paved the way for the usage of anti-TNF biologics to be delivered to the brain by a novel non-invasive perispinal route of delivery (perispinal administration). This work on TNF will markedly change medicine’s approach to treating traumatic brain injury (TBI), stroke, depression, neuropathic pain, CRPS, dementia, Alzheimer’s disease, and much more. It is our hope that the medical and scientific communities will be inspired and driven by the quest for knowledge, understanding, and alleviation of needless suffering, and thus embrace this game-changing treatment for brain injury-induced pathologies and subsequent disabilities.
To this end, we have established collaborations with the Institute of Neurological Recovery, where Dr. Edward Tobinick is successfully treating neurologic dysfunction using perispinal injection of a TNF blocker (Etanercept), procedures that are based on the founding team’s research findings. The founding team has personally witnessed Dr. Tobinick’s extraordinary clinical procedure in Boca Roton, FL. We have published this case study as well as two review articles (see attached CV) pertaining to this clinical application. These reports explain the success of this clinical application to alleviate neurologic pathology/dysfunction in terms of our novel molecular mechanism model of blocking the pathologic over-expression of brain-TNF and validate our in vitro work and animal model research. Dr. Tobinick’s clinical practice as well as present ongoing clinical trials validate the premise of our extensive basic research that show over-expressed TNF in the brain to be responsible for neuropathic pain and neurologic dysfunction. Dr. Tobinick’s off-label use (treatment of post-stroke/TBI neurological dysfunction) of FDA-approved etanercept via perispinal delivery (peripheral delivery and essentially non-invasive) is therapeutically effective and warrants rigorous scientific investigation as a treatment of TBI disability.