Blog Articles

Perispinal Delivery of CNS Drugs

Perispinal.Delivery.coverMay 2, 2016 (Los Angeles, Boca Raton): On April 27, 2016, the peer-reviewed review article entitled, Perispinal Delivery of CNS Drugs, by Edward Tobinick MD, published online in the scientific journal CNS Drugs. The article published in print in the June issue of the journal. The abstract of the article states:

Perispinal injection is a novel emerging method of drug delivery to the central nervous system (CNS). Physiological barriers prevent macromolecules from efficiently penetrating into the CNS after systemic administration. Perispinal injection is designed to use the cerebrospinal venous system (CSVS) to enhance delivery of drugs to the CNS. It delivers a substance into the anatomic area posterior to the ligamentum flavum, an anatomic region drained by the external vertebral venous plexus (EVVP), a division of the CSVS. Blood within the EVVP communicates with the deeper venous plexuses of the CSVS. The anatomical basis for this method originates in the detailed studies of the CSVS published in 1819 by the French anatomist Gilbert Breschet. By the turn of the century, Breschet’s findings were nearly forgotten, until rediscovered by American anatomist Oscar Batson in 1940. Batson confirmed the unique, linear, bidirectional and retrograde flow of blood between the spinal and cerebral divisions of the CSVS, made possible by the absence of venous valves. Recently, additional supporting evidence was discovered in the publications of American neurologist Corning. Analysis suggests that Corning’s famous first use of cocaine for spinal anesthesia in 1885 was in fact based on Breschet’s anatomical findings, and accomplished by perispinal injection. The therapeutic potential of perispinal injection for CNS disorders is highlighted by the rapid neurological improvement in patients with otherwise intractable neuroinflammatory disorders that may ensue following perispinal etanercept administration. Perispinal delivery merits intense investigation as a new method of enhanced delivery of macromolecules to the CNS and related structures.

Note added in July 2016: A related article, entitled “Perispinal Delivery of CNS Drugs: From Corning to Perispinal Etanercept”, published on July 9, 2016, on the Brain Immune Trends website, accessible by clicking here.

The full-text of the article is available by clicking on the link below:

Perispinal Delivery of CNS DrugsEdward Tobinick MD. CNS Drugs. 2016;30(6):469-80. do:10.1007/s40263-016-0339-2, published online 27 April 2016. (Download free full-text PDF).

Sunday Night (TV) News Story in Australia

“The New Stroke Treatment That’s Changing Lives”

Sunday Night (Australia), March 29, 2015


On March 29, 2015 the television news program “Sunday Night” in Australia aired a national news feature story about INR’s perispinal etanercept stroke treatment. The story was entitled “The New Stroke Treatment That’s Changing Lives”, and it is accessible online at this link:

Sunday Night “The New Stroke Treatment That’s Changing Lives”.

In the television feature, the clinical results of two patients treated at the INR by INR Los Angeles medical director Nancy Kim M.D., are depicted. The story was filmed both in Los Angeles at the time of treatment and in Australia, after each of the patients returned home.

Disclaimer: Individual results vary, not all patients respond. Continuing maintenance treatment may be necessary to maintain the clinical response. Treatment for this indication is off-label. Please see the Terms of Use. The method of treatment utilized is a patented invention of the INR. Issued and pending U.S. and foreign patents, including, but not limited to, U.S. 6419944, 6537549, 6982089, 7214658, 7629311, 8119127, 8236306, 8349323 and 8900583 all assigned to TACT IP, LLC; and Australian patent 758523.

Randomized, double-blind, placebo-controlled etanercept for Alzheimer's clinical trial results publish

Issue 10, volume 4, Supplement of Alzheimer’s and Dementia: Journal of the Alzheimer’s Association, Session 04-11-02, P273, entitled “The Safety and Tolerability of etanercept in Alzheimer’s disease (STEADI-09): A Phase II Double Blind Randomised Placebo Controlled Trial”, principal investigator Clive Holmes MD, University of Southampton, Southampton, United Kingdom, contains the first double-blind, randomized, placebo-controlled data supporting the therapeutic efficacy of etanercept for treatment of Alzheimer’s disease. The abstract of this study (full-text here) published in this issue in July 2014. The abstract concludes:

This study shows good tolerability and safety of Etanercept in the subjects with Alzheimer’s Disease. This study is also supportive of beneficial cognitive, behavior and activities of daily living in subjects taking subcutaneous Etanercept.”

A 2008 article in BBC News had previously discussed the favorable results of etanercept for treatment of Alzheimer’s disease in a study whose lead author was Edward Tobinick M.D. The article reported at the time that Clive Holmes MD was interested in taking on further research utilizing this treatment approach.

Further recognition of the scientific rationale for TNF inhibition in stroke models

May 10, 2014

Two scientists from the UCLA Department of Neurology have published a new research article entitled “Intracerebral hemorrhage in mouse models: therapeutic interventions and functional recovery“,  Metab Brain Dis. 2014 epub May 10.

The authors recognize intracerebral hemorrhage as a subtype of focal stroke and the most common form of brain hemorrhage. The authors explain,

With direct blood extravasation into brain, secondary inflammation is a substantial feature. Drugs which reduce neuroinflammation enhance functional recovery. Lei and colleagues targeted tumor necrosis factor alpha (TNF-alpha), a cytokine that is secreted by the microglia in response to injury and acts as a prime neuroinflammatory mediator causing progressive damage. A single dose of TNF-alpha antibody … showed evidence of reduced neuroinflammation and improved functional deficit….”

INR News and Links

For further information regarding the INR, please see the following sources, accessible by clicking on the links below:

Griffith University initiates a randomized, double-blind clinical trial using a TNF inhibitor for Alzheimer's disease

December 18, 2013 (Gold Coast, Australia): Today Griffith University, on their Alzheimer’s trial website, announced that the Griffith University Alzheimer’s Study has recently been granted full approval by the Human Research Ethics Committee as the first randomized double blind clinical trial to test perispinal etanercept  for dementia in Australian patients. More information here, on the Griffith website. The INR congratulates Griffith University and its scientists and physicians for their diligence and outstanding efforts that have enabled the initiation of this new study. The approval and initiation of this new study represents independent scientific support for the scientific rationale underlying this treatment approach that was invented and pioneered at the INR in Los Angeles.

Study provides new evidence for the efficacy of a TNF inhibitor for relief of persistent sciatica

November 1, 2013: A new randomized study published in the November 1, 2013 issue of the journal Spine (Freeman, B.J., et al., Randomized, Double-blind, Placebo-Controlled, Trial of Transforaminal Epidural Etanercept for the Treatment of Symptomatic Lumbar Disc Herniation. Spine (Phila Pa 1976), 2013. 38(23): p. 1986-94) provides new evidence for the efficacy of a TNF inhibitor for relief of persistent sciatica associated with lumbar disc herniation. Etanercept is a potent anti-inflammatory drug that is a selective blocker of an immune signaling molecule called TNF. Local perilesional methods of administration of etanercept, including epidural injection for treating sciatica associated with lumbar disc herniation were invented by Edward Tobinick M.D. more than a decade earlier (U.S. patent 6,419,944; 6,537,549; and others).

The new Spine study now constitutes the third published favorable clinical trial providing randomized, controlled trial (RCT) data of the efficacy of etanercept for treating sciatica. Dr. Tobinick was the first to publish human data reporting the effectiveness of etanercept for this indication in 2003, with a larger study published in 2004 (Tobinick, E. and S. Davoodifar, Efficacy of etanercept delivered by perispinal administration for chronic back and/or neck disc-related pain: a study of clinical observations in 143 patients. Curr Med Res Opin, 2004. 20(7): p. 1075-85).

Individual results can vary. See the Terms of Use.  Intractable disc-related low back and neck pain are important medical problems with significant unmet medical need.

Four randomized controlled clinical trials support the efficacy of a TNF inhibitor for disc-related pain

November 4, 2013:

U.S. patent 6,419,944 (inventor Edward Tobinick M.D., filed April 5, 2001) contained the first clinical report of rapid improvement in disc-related pain following the administration of perispinal etanercept. Now, more than a decade later, there are four favorable clinical trials that provide randomized, controlled trial (RCT) data supporting the efficacy of etanercept for treating disc-related pain. In 2013, data from two of these RCTs have been presented: the Nov 1 study by Freeman published in Spine; and the study conducted at Chiba University in Japan(Sainoh, T., et al., Intradiscal Administration of Tumor Necrosis Factor-Alpha Inhibitor, Etanercept, Clinically Improves Intractable Discogenic Low Back Pain: A Prospective Randomized Study, in International Society for the Study of the Lumbar Spine 40th Annual Meeting, May 2013). In 2012 the RCT by Ohtori reported positive etanercept data (Ohtori, S., et al., Epidural administration of spinal nerves with the tumor necrosis factor-alpha inhibitor, etanercept, compared with dexamethasone for treatment of sciatica in patients with lumbar spinal stenosis: a prospective randomized study. Spine (Phila Pa 1976), 2012. 37(6): p. 439-44). In 2009 the RCT performed at Walter Reed Army Medical Center provided favorable efficacy and human and animal safety data (Cohen, S.P., et al., Randomized, double-blind, placebo-controlled, dose-response, and preclinical safety study of transforaminal epidural etanercept for the treatment of sciatica. Anesthesiology, 2009. 110(5): p. 1116-26).

Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage

August 20, 2013:

A new basic science study from a research group at Duke provides new evidence supporting the rationale of TNF Inhibition following certain forms of stroke. The scientific rationale was discussed more than a decade earlier by Edward Tobinick in U.S. patent 6,419,934, filed September 5, 2000. On August 20, 2013, in the Journal of Neuroinflammation, the study authors  wrote: “Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH“. (Lei, B., et al., Tumor necrosis factor alpha antagonism improves neurological recovery in murine intracerebral hemorrhage. J Neuroinflammation, 2013. 10(1): p. 103). The background and conclusions of the abstract follow: Background: Intracerebral hemorrhage (ICH) is a devastating stroke subtype characterized by a prominent neuroinflammatory response. Antagonism of pro-inflammatory cytokines by specific antibodies represents a compelling therapeutic strategy to improve neurological outcome in patients after ICH. To test this hypothesis, the tumor necrosis factor alpha (TNF-alpha) antibody CNTO5048 was administered to mice after ICH induction, and histological and functional endpoints were assessed. Conclusions: Post-injury treatment with the TNF-alpha antibody CNTO5048 results in less neuroinflammation and improved functional outcomes in a murine model of ICH. See also: (Tobinick, E., Rapid improvement of chronic stroke deficits after perispinal etanercept: three consecutive cases. CNS Drugs, 2011. 25(2): p. 145-55; and Tobinick, E., et al., Selective TNF Inhibition for Chronic Stroke and Traumatic Brain Injury : An Observational Study Involving 629 Consecutive Patients Treated with Perispinal Etanercept. CNS Drugs, 2012. 26(12): p. 1051-70. Results can vary. Please see the Terms of Use.