This report confirms a previous study showing that the peri-spinal administration of TNF-alpha inhibitors dramatically reversed symptoms in patients with Alzheimer's disease. The new report shows a 55 percent reduction in risk of developing Alzheimer's disease in patients treated with infliximab, etanercept, and adalimumab. The reduction of inflammation in Alzheimer's disease caused by this class of drugs is under current investigation.
What is Tumor Necrosis Factor?
Tumor necrosis factor (TNF) is an immune system chemical known as a cytokine that contributes to inflammation in various autoimmune and inflammatory diseases. TNF is a critical component of the brain’s immune system network. Normally, TNF works to regulate the transmission of neural impulses. It’s suspected that in Alzheimer’s disease, increased levels of TNF interfere with signal regulation. Previous studies have shown that excess levels of TNF-alpha are found in the cerebrospinal fluid of patients with Alzheimer’s disease. In rheumatoid arthritis, excess amounts of TNF are seen in affected synovium.
Use of TNF Inhibitors
Many autoimmune diseases including rheumatoid arthritis, Crohn’s disease, psoriasis, uveitis and other complications in Behcet’s disease, and ankylosing spondylitis, are routinely treated with TNF inhibitors. TNF inhibitors, which are also called biologics or biologicals, reduce the production of TNF.
In these autoimmune disorders, TNF inhibitors accomplish this by suppressing the activity of B-lymphocytes related to inflammation. Persistent, chronic inflammation causes a number of complications including amyloidsosis. In amyloidosis, excess deposits of amyloid protein infiltrate and damage various organs. In Alzheimer’s disease, amyloid deposits are found in the brain.
In reducing inflammation in autoimmune disorders, TNF-alpha inhibitors such as etanercept (Enbrel) reduce symptoms of inflammation and disease progression. In the UCLA study, perispinal injections of etancercept to Alzheimer’s patients showed dramatic improvement within minutes. The new study confirms that the incidence of Alzheimer’s disease is reduced in patients with rheumatoid arthritis using TNF-inhibitors. This effect is not seen in patients using other arthritic remedies such as prednisone, rituximab and sulfasalazine.
Relapses and Problems in Autoimmune Disease
However, not all patients with rheumatoid arthritis and other autoimmune disorders respond well to TNF-alpha inhibitors during and after therapy. One reason is the immunogenicity of these drugs. That is, they can cause the development of autoantibodies that attack these drug molecules. Chimerically synthesized drugs show greater immunogenicity than completely human-derived drugs. In RA, infliximab can cause autoantibody production in 12-44 percent of patients, whereas autoantibodies targeted against etanercept are reported to occur in 0-18 percent of subjects. In addition, tuberculosis and some other granulomatosis infections are seen more frequently in in patients treated with monoclonal antibodies compared to patients treated with soluble TNF inhibitors.
The problems seen with TNF inhibitors in autoimmune disorders are helpful when evaluations of these drugs are made in other conditions. With these aims in mind, further studies to evaluate the usefulness of TNF inhibitors in Alzheimer’s disease are warranted.
Léia CR Silva; Luciena CM Ortigosa; Gil Benard. 2010. "Anti-TNF-α Agents in the Treatment of Immune-mediated Inflammatory Diseases: Mechanisms of Action and Pitfalls". Immunotherapy, November 2010, Vol. 2 (6): 745-748.
Reversal of Alzheimer’s Symptoms Within Minutes in Human Study. 2008. Science Daily.
"Anti-TNF Therapies for Rheumatoid Arthritis Could Reduce Alzheimer’s Risk". Press Release. American College of Rheumatology. Nov 2010.
Emi, Aikawa, de Carvalho, J., Artur, Almedia, and E. Bonfa. "Immunogenicity of Anti-TNF-alpha agents in autoimmune diseases". Clinical Reviews in Allergy and Immunology 2010 April; 38(2-3): 82-89.