Document 0651
 DOCN  M9590651
 TI    PML and a tale of two drug companies. Clearinghouse, P.O. Box 6003,
       Rockville, MD 20849-6003. 800-458-5231 ext. 5023.
 DT    9509
 SO    Notes Undergr. 1995 Winter;(no 29):4-6. Unique Identifier : AIDSLINE
       AIDS/95700304
 AB    PML is a rare disease that destroys myelin tissue in the central nervous
       system and causes lesions in the brain. Probably caused by the JC virus,
       the disorder can proceed rapidly. Currently there is no treatment for
       PML. However, Dr. Khalili at Thomas Jefferson University published
       research showing that topotecan, an analogue of campthotecin (derived
       from the bark of a chinese tree), suppresses the JC virus in the test
       tube at low doses. Although this is promising, it is unclear how well
       the drug crosses the blood-brain barrier or even if targeting the JC
       virus is the best way to stop PML. The drug is in phase II/III cancer
       trials. Although toxic, topotecan appears to inhibit the JC virus at
       lower doses than for cancer. SmithKline Beecham (SKB) owns the license
       to develop topotecan. SKB has had little interest in AIDS research since
       their protease inhibitor did not pan out. Responding to activists, SKB
       announced that they are pursuing topotecan as an anti-HIV drug, with
       studies opening this spring. There are other derivatives of
       campthotecin, 9-A-C and CPT-11 or irinotecan. 9-A-C does not work in the
       test tube; however, CPT-11, a cancer drug from Japan, is being studied
       by Upjohn. Upjohn supplied Dr. Khalili with CPT-11 and SN-38. Dr.
       Khalili found that both inhibited the JC virus in the test tube, and
       that SN-38 was a better JCV inhibitor than topotecan. Dr. Sidney Huff,
       Georgetown, has requested and received compassionate use for two PML
       patients.
 DE    AIDS-Related Opportunistic Infections/*DRUG THERAPY
       Albendazole/*THERAPEUTIC USE  Blood-Brain Barrier  Camptothecin/ANALOGS
       & DERIVATIVES/PHARMACOLOGY/PHARMACOKINETICS/  *THERAPEUTIC USE  Drug
       Industry  Human  Leukoencephalopathy, Progressive
       Multifocal/COMPLICATIONS/*DRUG  THERAPY  Microspora Infections/*DRUG
       THERAPY  Polymerase Chain Reaction  Polyomavirus hominis 2/DRUG
       EFFECTS/GENETICS/ISOLATION & PURIF  NEWSLETTER ARTICLE

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       protected by Copyright Law (Title 17, U.S.Code).