Perispinal injection of etanercept can produce dramatic and sustained improvement of symptoms of Alzheimer's disease within minutes of administration

Perispinal injection of etanercept can produce dramatic and sustained improvement of symptoms of Alzheimer's disease within minutes of administration, according to an article published online January 9 by the Journal of Neuroinflammation.

Although the article discusses one patient in detail, many other patients with mild to severe Alzheimer's disease received the treatment and all showed sustained and marked improvement.

Etanercept (trade name Enbrel) binds and inactivates excess tumor necrosis factor alpha (TNF alpha), a cytokine previously shown to be a critical component of the brain's immune system. Etanercept is approved in the U.S. to treat a number of immune-mediated disorders.

Normally, TNF alpha finely regulates transmission of neural impulses in the brain. The authors hypothesized that elevated cytokine levels in patients with Alzheimer's disease interfere with this regulation. To reduce TNF alpha levels, the authors gave patients an injection of the anti-TNF therapeutic agent etanercept. Excess TNF alpha has been documented in the cerebrospinal fluid of patients with Alzheimer's disease.

The Neurotechnology Industry Organization has recently selected new treatment targets revealed by neuroimmunology (such as excess TNF alpha) as one of the top 10 Neuroscience Trends of 2007. The Dana Alliance for Brain Initiatives chose the pilot study using perispinal etanercept for Alzheimer's disease for inclusion and discussion in their 2007 Progress Report on Brain Research.

The lead author of the study, Edward Tobinick MD, is an assistant clinical professor of medicine at the University of California, Los Angeles and director of the Institute for Neurological Research, a private medical group in Los Angeles. Hyman Gross, MD, clinical professor of neurology at the University of Southern California, was co-author.

The study was accompanied by an extensive commentary by Sue Griffin, PhD, director of research at the Donald W. Reynolds Institute on Aging at the University of Arkansas for Medical Sciences (UAMS) in Little Rock and at the Geriatric Research and Clinical Center at the VA Hospital in Little Rock.

Griffin published a landmark study in 1989 describing the association of cytokine overexpression in the brain and Alzheimer's disease. Her research helped pave the way for the findings of the present study. Griffin has recently been selected for membership in the Dana Alliance for Brain Initiatives, a nonprofit organization of more than 200 leading neuroscientists, including ten Nobel laureates.

"It is unprecedented that we can see cognitive and behavioral improvement in a patient with established dementia within minutes of therapeutic intervention," said Griffin. "It is imperative that the medical and scientific communities immediately undertake to further investigate and characterize the physiologic mechanisms involved. This gives all of us in Alzheimer's research a tremendous new clue about new avenues of research, which is so exciting and so needed in the field of Alzheimer's. Even though this report predominantly discusses a single patient, it is of significant scientific interest because of the potential insight it may give into the processes involved in the brain dysfunction of Alzheimer's."

The new study, entitled "Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration," and the accompanying commentary, entitled "Perispinal etanercept: Potential as an Alzheimer's therapeutic," are available on the Web site of the Journal of Neuroinflammation, at http://www.jneuroinflammation.com.


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