Perispinal etanercept: a new therapeutic paradigm in neurology

An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers

“…Supporting the notion that AβO-induced neuronal insulin resistance derives from an inflammatory response mediated by TNF-α, the TNF-α-blocking antibody infliximab protected neurons against oligomers. Used to treat inflammatory diseases (62), infliximab and etanercept, a TNF-α-blocking recombinant protein, have been proposed as novel therapeutic agents to combat insulin resistance in type 2 diabetes (63) and memory decline in AD (64). By defending neurons from oligomer-induced dysregulation of insulin signaling, infliximab treatment may constitute a novel approach to prevent memory impairment in AD.…”

Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales

“…Because the intracerebroventricular route is a precarious one, unsuited to regular administration to the same patient, a number of ways to circumvent this problem are being developed to widen the use of these highly successful biological agents to a new patient group. The earliest of these is a novel approach termed the perispinal route (Tobinick et al, 2006(Tobinick et al, , 2010(Tobinick et al, , 2012. Its logic depends on 1) a short period of head-down tilting to gain a gravitational advantage, 2) an awareness of anatomy of Batson's plexus [a valveless venous system that surrounds the spinal column in continuum with the choroid plexus (Nathoo et al, 2011)], and 3) knowledge of the effect of acute hypertension on choroid plexus permeability [a 30-fold increase in albumin in CSF within 10 min of pharmacologically induced acute local hypertension (Murphy and Johanson, 1985)].…”

Effective Stepwise Anti-inflammatory Treatment for Markedly Disabling Neuropsychiatric Comorbidities: A Case Report

“…However, she remained emotionally reactive and irritable, and her ability to perform daily activities was still erratic, as she continued to struggle with periodic head pain, anger, and/or episodes of depression, and was cognitively still somehow limited. Therefore, approximately six months after completion of the TMS/ketamine treatment series, another line of intervention was started, namely the PSE injections [18][19][20]33] (The method of perispinal administration of etanercept was used under license from the patent holder, TACP IP, LLC. ).…”

“…Therefore, the decision was made to start PSE. This technique works in part by inducing TNF-alpha modulation directly to the central nervous system, thus normalizing the inflammatory response [18][19][20]33]. The subsequent clinical amelioration and marked improvement on the SPECT functional imaging validated this decision.…”

“…Additionally, ketamine is known to act as a TNF-alpha inhibitor, thus favoring an anti-inflammatory effect [17]. PSE injections induce tumor necrosis factor (TNF)-alpha modulation directly to the central nervous system and act to normalize the inflammatory response in stroke, traumatic brain injury, and encephalopathic conditions [18][19][20]. The SPG is known to decrease migraine intensity [21] and also to have an anti-inflammatory effect [22].…”