NEW ALZHEIMER'S TREATMENT WORKS IN MINUTES
By Jonathan M. Gitlin
arstechnica.com
January 10, 2008

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Alzheimer's disease is a growing concern among our aging populations. As people live longer lives, diseases of old age become increasingly common. Perhaps, as with obesity, diabetes, atherosclerosis, and other common modern maladies, there are also lifestyle or environmental factors at play. Alzheimer's, unlike those ailments of the body, has had little in the way of useful therapeutics, instead only offering the promise of an inevitable mental decline.

One reason for the lack of effective Alzheimer's drugs has been our understanding of the mechanisms involved in how the disease works. The widely accepted view has been that certain proteins that are present in nerve cells begin to aggregate together, forming lesions. Potential therapies often focus on a neurotransmitter, acetylcholine (ACh), and often have unpleasant side effects.

More recently, neuroscientists have been looking not at the neurons, but the cells that surround them as an important component of the disease. Glial cells are most of the cells in the brain that aren't neurons, and they fulfill a range of specialized functions from forming myelin to housekeeping in the brain. Some glia envelope neuronal synapses, the junctions between nerves where neurotransmitters signal from one to another, and it's these cells that are now increasingly thought to be critical in Alzheimer's.

What's surprising is the involvement of a molecule we thought we knew quite well. Most scientists working in biomedical research would be familiar with a cytokine called Tumor Necrosis Factor (TNF)-α. TNFα is a signaling protein that is deeply involved in inflammation, and drugs that act on the TNFα pathway are increasingly being used as treatments for autoimmune diseases. But as it turns out, in the brain TNFα is used by glial cells as a gliotransmitter, and increased levels of TNFα in the brain, outside of the normal physiological levels, results in impairment of synaptic function.

And that appears to provide a therapeutic avenue, thanks to those new TNFα drugs we have developed. The Journal of Neuroinflammation carries a case report of the rapid mental improvement of an Alzheimer's patient following spinal infusion of a drug called etanercept. Etanercept is a protein drug that binds to TNFα and neutralizes it. Within just two hours of initial treatment with the drug, the patient showed marked improvement on a range of cognitive tests, and following a short series of repeat treatments, continued to improve. The authors of the study have been using this treatment for several years now, and have published other case studies also showing a remarkable mental improvement.

While this case report gives cause for optimism, it must be noted that the research is still preliminary; double-blind trials have not been performed, and the case reports don't examine biomarkers of Alzheimer's disease. Nevertheless, given the possibility of reversing this terrible disease, it seems a foregone conclusion those double-blind trials are in the works.