Randomized controlled trial validating the use of perispinal etanercept to reduce post-stroke disability has wide-ranging implications

ABSTRACT

Developing effective drug treatments for neurodegenerative disorders has always been hamstrung by the accepted inability of large molecules (roughly those with a molecular weight greater than 600 Daltons) to cross the blood-brain barrier (BBB) in therapeutic quantities when administered systemically. The dogma has been that a simple, noninvasive way to accomplish this goal is not possible with many agents, including biologicals, because they are too large. Various novel technologies to breach the BBB have been attempted, but with little success. A randomized double-blind, placebo-controlled clinical trial (RCT) administering a widely used anti-tumor necrosis factor (TNF) biological, etanercept, given via perispinal injection, which bypasses the BBB, turns this dogma on its head. This new trial holds much promise for stroke survivors, as well as having implications for developing treatments based on other large molecules for this and other brain disorders.

KEYWORDS:

• Blood-brain barrier
• etanercept
• double-blind controlled trial
• perispinal route of administration
• post-stroke therapy
• TNF

Article highlights

• The blood-brain barrier has effectively excluded the brain from much of the biotech revolution. Much research has attempted to clear this roadblock, but without success to date.

• Perispinally injected etanercept, which involves injecting this anti-TNF biological into the cerebrospinal venous system before a short period of head-down tilt, has been commonly used by the originator of the technique since 2011 to treat post-stroke syndromes. Without witnessing the treatment, the Big Pharma owners of the patent for etanercept and the American Academy of Neurology have actively discouraged a trial.

• Funding from the Australia public has made possible the first formal controlled trial of perispinal etanercept on post-stroke patients. Within the goals set, the outcome was statistically significant, often markedly so.

• If confirmed in larger trials, this technique will likely have widespread usefulness in getting larger pharmaceuticals, particularly biologicals, into the brain in many different brain disease states, including cancer.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Comments were received from three further referees

Reviewer disclosures

A reviewer on this manuscript has disclosed a direct financial conflict of interest with respect to the subject of this article. The three further peer reviewers who provided comments on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.