Prospects for therapeutic vaccination with glatiramer acetate for neurodegenerative diseases such as Alzheimer's disease

Abstract

Neurodegenerative diseases, whatever their primary causes, are characterized by certain common features, one of which is their self‐perpetuating nature. The ongoing progression of the disorder is due to the effects of destructive self‐compounds, whose presence in the tissues is an outcome of the early phase of the disease and which gradually destroy remaining functional neurons. Studies in our laboratory have led to the recent formulation of a novel concept of protective autoimmunity as the body's mechanism of defense against these destructive self‐compounds. This autoimmune response to central nervous system (CNS) insults is mediated by T‐cells and presumably operates by activating and regulating local microglia and infiltrating macrophages (inflammatory response) to carry out their function of clearing destructive material from the tissue at risk. We suggest that a well‐controlled autoimmunity counteracts and overcomes the destructive effects of the potentially harmful self‐compounds, at the cost of some loss of tissue. An additional risk to the individual is the induction of an autoimmune disease, which is likely to occur if the autoimmune response is malfunctioning. An optimal balance of the various factors will lead to an outcome of maximal benefit at minimal cost to the tissue. A procedure for safely boosting the autoimmune response, by vaccination with a weak self‐crossreactive antigen such as glatiramer acetate (also known as Cop‐1) was found to protect rats from glutamate toxicity, a major mediator of the spread of damage and a well‐known causative factor in neurodegenerative disorders. Cop‐1, when administered according to a different regimen, is an FDA‐approved drug for the treatment of multiple sclerosis. Different formulations of the same drug can therefore be used to treat two extreme manifestations of chronic degenerative diseases of the CNS. Drug Dev. Res. 56:143–149, 2002. © 2002 Wiley‐Liss, Inc.

Neurodegeneration and Neuroprotection in Glaucoma: Development of a Therapeutic Neuroprotective Vaccine

“…It is important to note that the proposed vaccine will incorporate Cop-1 in a different formulation and according to a different regimen from those used for treating an autoimmune disease, as the same compound activates different mechanisms in different regimens. 31,32 Since degeneration is a highly complex process, in which the players are affected by a multiplicity of factors (some of them mutually contradictory), therapeutic intervention by a single factor is likely to prove only partially effective. Activation of the patient's own immune cells may provide comprehensive protection that is both self-regulating and self-limiting.…”