New research into brain tissue injury (from stroke and brain injury) has found that although it was once assumed that all of the non functioning areas of brain after injury were dead, it has now been confirmed that some of this non functioning brain tissue is inflammed. This has led to exciting new developments in treatment. One of these developments is a treatment called Perispinal Etanercept.
What is Perispinal Etanercept Treatment ? Pioneering treatment in USA for people who have suffered stroke or brain injury is having unprecedented favourable results. Many Australians and people from other parts of the world are travelling to the Institute of Neurological Recovery in California and Florida for treatment that is not yet available in Australia, New Zealand – or in other parts of the world.
Scientists looking at inflammatory processes within the brain following injury, including many in Australia, have for decades shown that this inflammation not only increases symptoms of brain tissue injury but is responsible for a whole range of symptoms, quite separate to the initial injury. Despite being aware of the problems these inflammatory processes cause, until a few years ago, there was no treatment available.
To provide a background to both the brain inflammation and the new treatment, it is important to understand the basic science of how the inflammation develops. Humans (and other animals) have a protein in our bodies called Tumour Necrosis Factor (TNF), which is important in maintaining our normal immune function. Like other aspects of our health, there is a balance of TNF that is needed to maintain optimum health, including a healthy brain, but if we have too much TNF in our bodies we develop inflammatory diseases. Thankfully there are drugs like Etanercept that are commonly used to treat such conditions, such as rheumatoid arthritis. The way Etanercept works is that when injected under the skin twice a week, it neutralizes the excessive amounts of TNF and therefore reduces the inflammation in our bodies. This treatment is currently available as “on-label” treatment in Australia.
In order to protect our brain, our bodies have a super protective barrier around the brain and spinal cord, which screens out bacteria and most toxic substances. Unfortunately the molecule size of Etanercept is too large to cross the blood brain barrier efficiently, and is therefore unlikely to be effective in being able to treat the inflammation in the brain following brain tissue injury by being injected under the skin in the normal manner.
Dr Tobinick, at the Institute of Neurological Recovery has developed an innovative way (called Perispinal) of injecting Etanercept that is designed to deliver the molecule into the area drained by a particular blood vessel complex to improve its selective delivery into the brain.
Following Perispinal Etanercept Treatment, many patients start to experience positive effects from the Etanercept within a few minutes, although the benefits from the TNF neutralizing effects can keep increasing for several weeks after the treatment is given. Results from the treatment are very individual, due to variability in the nature and extent of each brain tissue injury. The types of improvements include improvements in mobility, speech, swallowing, memory, concentration, taste, vision, hearing – all depending on the site and extent of the initial injury and subsequent inflammation. Similarly, reductions in muscle spasticity and pain, recovery of areas of sensation loss, and improvements in cognition, behavioral function, and continence are also common areas of significant improvement. The results from this treatment have been shown to be robust even if the treatment is administered many years post-injury. There is individual variability in response to treatment. Some people with stroke and brain injury experience additional gains with second or third treatments. The traditional medical view is that all affected brain areas are permanently damaged, but the literature, and current clinical observation, say otherwise.
The use of Etanercept for brain injury is off-label. This simply means that although registered for treating other diseases, such as rheumatoid arthritis (where subcutaneous injection works) in Australia and elsewhere, it is not yet registered for brain damage diseases, so this use is not printed on the label of the bottle. The responsibility is on the medical practitioner to use informed judgement before using a drug for an off-label purpose, and provided scientific evidence, safety, and other treatment options are taken into account, such use is legal and common. Despite the good evidence that is accumulating in favour of its use, etanercept for brain damage, like all off-label drug usage, of course awaits more rigorous clinical trials before it can be officially recommended, i.e. become on-label.
Unfortunately the Perispinal mode of delivery that is necessary for brain entry is still novel to many medical practitioners, so they need to have it explained and demonstrated, which has not yet happened in this part of the world. In the meantime, people with brain injury and stroke continue to travel to the US, at considerable travel cost and effort, and although treatment response can vary, there are many validated individual reports of patients regaining lost function and improved quality of life for both themselves and their families.
The proposed Griffith University School of Medicine Perispinal Etanercept Clinical Trial for Stroke will provide valuable data for decision makers, such as the Therapeutic Good Administration , in deciding if this treatment should be made available in Australia and in other parts of the world.
The Stroke Recovery Trial Fund LTD charity has been established for this exact purpose – to raise the $AUD 300,000 required to fund the Griffith University School of Medicine Perispinal Etanercept Clinical Trial for Stroke. If successful the clinical trial will help facilitate the Therapeutic Goods Administration making the Perispinal Etanercept treatment available in Australia and other countries.
Clark, I. A., Alleva, L. M., & Vissel, B. (2010). The roles of TNF in brain dysfunction and disease. Pharmacology & therapeutics, 128(3), 519-548
Tobinick E: Perispinal etanercept for neuroinflammatory disorders. (2009). Drug Discovery Today 14(3-4):168-177.
Tobinick E, Kim NM, Reyzin G, Rodriguez-Romanacce H, DePuy V: (2012). Selective TNF inhibition for chronic stroke and traumatic brain injury: an observational study involving 629 consecutive patients treated with perispinal etanercept. CNS Drugs, 26(12):1051-1070.