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Drug therapy in human and experimental transmissible spongiform encephalopathy

From the Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.

Address correspondence and reprint requests to Dr. Paul Brown, Building 36, Room 4A-19 (MSC-4123), National Institutes of Health, Bethesda, MD 20892-4122; e-mail: brownp{at}ninds.nih.gov

During the past 30 years, over 60 different chemical compounds have been used to treat experimental animals infected with transmissible spongiform encephalopathies (TSE), including a wide variety of anti-infectious agents, immunomodulating drugs, and chemicals interacting with the lympho-reticular system. Some compounds achieved a prolongation of the incubation period, but this effect decreased or disappeared when they were administered at or near the onset of symptomatic disease. Recent in vitro and tissue culture studies support earlier speculation about the importance of a chemical structure containing both water-soluble and lipid-soluble components, evidently as a means of interaction with the misfolded membrane-bound ‘prion’ protein. A number of compounds shown to eliminate the protein (or infectivity) in TSE-infected tissue cultures are the subject of ongoing studies in animals, and are under consideration for human drug trials. As with other recalcitrant infections, combinations of drugs with different modes of action are likely to be necessary for any effective therapy. Also, very recent work in developing antibodies that can neutralize in vitro infection (and, in conjunction with genetic engineering, in vivo infection) has renewed interest in the strategies of both active and passive immunization.

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