New study highlights importance soluble proteins, called cytokines, in Alzheimer's

Jan 10 2008

An extraordinary new scientific study, which for the first time documents marked improvement in Alzheimer's disease within minutes of administration of a therapeutic molecule, has just been published in the Journal of Neuroinflammation.

This new study highlights the importance of certain soluble proteins, called cytokines, in Alzheimer's disease. The study focuses on one of these cytokines, tumor necrosis factor-alpha(TNF), a critical component of the brain's immune system. Normally, TNF finely regulates the transmission of neural impulses in the brain. The authors hypothesized that elevated levels of TNF in Alzheimer's disease interfere with this regulation. To reduce elevated TNF, the authors gave patients an injection of an anti-TNF therapeutic called etanercept. Excess TNF-alpha has been documented in the cerebrospinal fluid of patients with Alzheimer's.

The new study documents a dramatic and unprecedented therapeutic effect in an Alzheimer's patient: improvement within minutes following delivery of perispinal etanercept, which is etanercept given by injection in the spine. Etanercept (trade name Enbrel) binds and inactivates excess TNF. Etanercept is FDA approved to treat a number of immune-mediated disorders and is used off label in the study.

The use of anti-TNF therapeutics as a new treatment choice for many diseases, such as rheumatoid arthritis and potentially even Alzheimer's, was recently chosen as one of the top 10 health stories of 2007 by the Harvard Health Letter.

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

The lead author of the study, Edward Tobinick M.D., 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, M.D., clinical professor of neurology at the University of Southern California, was co-author.

The study is accompanied by an extensive commentary by Sue Griffin, Ph.D., 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, who along with Robert Mrak, M.D., chairman of pathology at University of Toledo Medical School, are editors-in-chief of the Journal of Neuroinflammation.

Griffin and Mrak are pioneers in the field of neuroinflammation. 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.”