Update on Progressive Multifocal LeukoencephalopathyMarch 1997 A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information! Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection of the central nervous system that occurs in 2-7% of individuals with AIDS. PML is caused by JC virus, a polyomavirus that belongs to the papovavirus family of viruses. A small number of cases have been caused by papovaviruses that were more similar to SV-40 virus. About 70% of HIV seronegative individuals [Taguchi F et al, Microbiol Immunol 26:1057, 1982] and nearly 65% of patients with AIDS [Gillespie S et al, Ann Neurol 30:597,1991] produce antibodies against JC virus, indicating prior infection. Among healthy individuals primary infection with JC virus causes no known disease, with the virus assuming a latent state in the kidney. However, in the setting of chronic immunosuppression the infection may become reactivated, and JC virus may subsequently reach the nervous system by transport within infected B cells [Tornatore C, et al Ann Neurol 31:454, 1992].
Treatment involves optimizing antiretroviral therapy, which may lead to clinical stabilization or remission in some cases. Cytosine arabinoside (Ara-C) has not been demonstrated to be effective in treating PML, and interferon-alpha treatment may or may not be of benefit [Berger JR et al, Neurology 42(Suppl 3):257,1992; Huang S et al, 4th Conf. on Retroviruses and Opportunistic In-fections 4:127,1997]. A clinical trial is in progress using the topoisomerase inhibitor, topotecan hydrochloride, which has been demonstrated to inhibit the replication of JC virus in infected glial cells in culture [Kerr DA, et al Virology 196:612, 1993] and to suppress replication of HIV [Li C, et al PNAS, USA 90:1839, 1993]. This study is being sponsored by Smith Kline Beecham Pharmaceuticals and involves the administration of topotecan to patients with PML who do not have a history of prior treatment for the infection. Patients are currently being enrolled at the Johns Hopkins Hospital with other U.S. sites in Los Angeles, San Francisco/Berkeley, Miami, and New York and a European site in Paris, France. A note from TheBody.com: The field of medicine is constantly evolving. As a result, parts of this article may be outdated. Please keep this in mind, and be sure to visit other parts of our site for more recent information! ![]()
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