A Review of Immunotherapy for Alzheimer's Disease

Why build a completely new method of removing unwanted proteins or destroying unwanted cells, when a system capable of these tasks already exists in the body? That is the idea behind the many different forms of immune therapy, technology platforms that will come to be commonplace in medicine over the next few decades. Here is an open access review of the recent past and near future approaches to enlisting a patient's immune system to treat Alzheimer's disease:

Vaccination has been an instrument in the tool chest of the clinician since the late 18th century when Edward Jenner first used the related cowpox virus to immunize patients against small pox. The basic concept of active immunization is to prime the immune system to recognize an antigen as a foreign protein in order to mount a response against it. It has only been recently that investigators have attempted to utilize the human immune system to rid the body of potentially harmful or toxic proteins that are endogenously produced.

Alzheimer's disease (AD) is an incurable, progressive, neurodegenerative disorder affecting over 5 million people in the US alone. This neurological disorder is characterized by widespread neurodegeneration throughout the association cortex and limbic system caused by deposition of resulting in the formation of plaques and tau resulting in the formation of neurofibrillary tangles. Active immunization for Aβ showed promise in animal models of AD; however, the models were unable to predict the off-target immune effects in human patients. A few patients in the initial trial suffered cerebral meningoencephalitis.

Recently, passive immunization has shown promise in the lab with less chance of off-target immune effects. Several trials have attempted using passive immunization for Aβ, but again, positive end points have been elusive. The next generation of immunotherapy for AD may involve the marriage of anti-Aβ antibodies with technology aimed at improving transport across the blood-brain barrier (BBB). Receptor mediated transport of antibodies may increase central nervous system exposure and improve the therapeutic index in the clinic.

Link: http://journal.frontiersin.org/Journal/10.3389/fnagi.2014.00114/full


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