Advances in Antiviral Therapy for Subacute Sclerosing Panencephalitis

Abstract

Subacute sclerosing panencephalitis (SSPE) is a late-onset, intractable, and fatal viral disease caused by persistent infection of the central nervous system by a mutant strain of the measles virus. Ribavirin intracerebroventricular therapy has already been administered to several SSPE patients in Japan based on fundamental and clinical research findings from our group, with positive therapeutic effects reported in some patients. However, the efficacy of this treatment approach has not been unequivocally established. Hence, development of more effective therapeutic methods using new antiviral agents is urgently needed. This review describes the current status of SSPE treatment and research, highlighting promising approaches to the development of more effective therapeutic methods.

Keywords: SSPE; antiviral agent; ribavirin; therapy.

Figure 1

Measles virus genome showing the most common mutations found in SSPE cases. Genes that are mutated in many SSPE viruses compared to wild measles viruses are shown in gray.

Figure 2

Amino acid mutations in viruses derived from brains of mice with persistent. Measles Virus infection. The genes are listed on the horizontal axis. Each horizontal axis tick represents 50 amino acids. The number of amino acid mutations is presented on the vertical axis. Among the 10 clones, when any 1 clone had an amino acid mutation at a position, it was counted as one mutation. Overlapping mutations at the same position in multiple clones were counted as a single mutation [33].

Figure 3

Ribavirin concentration in the cerebrospinal fluid. (A) Expected and observed ribavirin concentrations in the cerebrospinal fluid (CSF) following repeated intraventricular administration (cyclic administration therapy). In case 1, ribavirin concentrations in the CSF were maintained throughout at levels sufficient for complete inhibition, but this was not done in case 2. The arrows indicate points of time when ribavirin was administered. CSF was collected by lumbar tap just before ribavirin administration [79]. (B) Ribavirin concentrations in the CSF following continuous intraventricular administration (continuous administration therapy). CSF was collected by lumbar tap 3–10 days after the start of ribavirin administration or at the time of saline substitution. Bars show the mean ribavirin concentration and standard error. Representative case is shown [82].

Figure 4

Protocol for ribavirin continuous infusion therapy using a continuous infusion pump. Patients were given ribavirin and interferon-α using a subcutaneous continuous infusion pump with oral administration of inosine pranobex (continuous administration therapy). At the start of the treatment, 1–2 mg/kg per day was used as the initial ribavirin dosage. Ribavirin dosage was raised according to its concentration in CSF and treatment cycles were repeated as maintenance doses [82].