Methods for Prevention and Treatment of Polyomavirus Infection or Reactivation (E-179-2007)

Available for licensing and commercial development are methods of using Tranilast [N-(3',4'-dimethoxycinnamoyl)anthranilic acid] in the prevention and treatment of human polyomavirus infection. Treatment with Tranilast decreases viral protein expression for two human polyomavirus species, JC virus (JCV) and BK virus (BKV). Furthermore, the increase in JCV/BKV protein production observed upon the addition of TGF-beta could also be effectively abolished by Tranilast co-treatment. This is of relevance because TGF-beta has previously been demonstrated to increase during immunosuppressive conditions, including HIV infection and kidney transplantation.

JCV is responsible for demyelization of the central nervous system, which is observed in cases of progressive multifocal leukoencephalopathy (PML). PML is most frequently seen in patients with HIV/AIDS, but is also a contributing factor in fatalities in patients with leukemia, lymphoma, and connective tissue diseases, in addition to individuals receiving immunosuppressive therapy for autoimmune disorders or prevention of transplant rejection. BKV is associated with serious clinical syndromes such as viruria and viremia, ureteral ulceration and stenosis, and hemorrhagic cystitis and has a causative role in polyomavirus-associated nephrophathy in as many as 10% of all renal transplant recipients. Currently, there are no effective antiviral agents available to treat these opportunistic infections. In all observed cases, activation of either JCV or BKV in immunosuppressed patients has resulted in fatalities.