PREVENTION OF AUTOIMMUNE DEMYELINATION IN NONHUMAN-PRIMATES BY A CAMP-SPECIFIC PHOSPHODIESTERASE INHIBITOR

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human di sease multiple sclerosis. We evaluated rolipram, a type IV phosphodies terase inhibitor, for its efficacy in preventing EAE in the common mar moset Callithrix jacchus. In a blinded experimental design, clinical s igns of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys tha t received rolipram (10 mg/kg s.c. every other day) beginning 1 week a fter immunization, In controls, signs of EAE were associated with deve lopment of cerebrospinal fluid pleocytosis and cerebral MRI abnormalit ies, In the treatment group, there was sustained protection from clini cal EAE, transient cerebrospinal fluid pleocytosis in only one of thre e animals, no MRI abnormality, and marked reduction in histopathologic findings, Rolipram-treated and control animals equally developed circ ulating antibodies to myelin basic protein, Thus, inhibition of type I V phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease.