Progressive Multifocal Leukoencephalopathy (PML), a demyelinating disease of the Central Nervous System (CNS), is determined by widespread lesions due to infection of oligodendrocytes by a human polyomavirus (papovavirus family) called the JC virus after John Cunningham, from whom it was first isolated. PML is found almost exclusively in individuals who are immunosuppressed: with AIDS, hematological, lymphoreticular malignancies, autoimmune rheumatological disease, multiple sclerosis (secondary to immunosuppressive treatment) and in those undergoing organ transplantation. The immune therapies with monoclonal antibodies including Natalizumab, rituximab and other immunosuppressants including prednisone, methotrexate, cyclophosphamide and cyclosporine may also be initiating factors in the development of PML.
Based on incidence rates, there are 35,000 yearly cases of HIV-associated PML globally, and there were nearly 5,000 cases of medication associated PML reported to the FDA in 2009. Less than ten percent of patients recover without any treatment, and currently, no therapeutics have been found to directly alter the course of JC virus infection/improve prognosis of PML afflicted patients.
RAP101 has been shown to have an anti-viral effect on the JC virus in PML patients. We have completed pre-clinical experiments in human glial cells demonstrating dose ranging and the effect of RAP101 on the JCV. In addition 20 Emergency INDs and 4 patients in a Pilot Phase 1 IND are completed. We are currently in the process of filing a Phase 2/3 IND for this Orphan Indication.