Development of therapeutic strategies

UltraMab

Development of methods to detect prions in human and animal biological fluids & organs

2010: 1 year / Grant: 40 000 euros

Project: The project named “UltraMab” proposed to develop new anti-PrP antibodies of high purity and affinity. The idea was to derive the antibodies from hybridoma devoid of cellular PrP to avoid any antibody neutralization. The team also planed to use these antibodiesfor the treatment of prion diseases. As antibodies could be toxic because of the occurrence of an immunological reaction, the antibody parts that interact with the immune system could be removed.

Main results and related published data: Following the production of new antibodies that appeared to detect PrPC and PrPTSE well, some of them were tested for therapeutic purposes and were shown to be toxic. Additional experiments determined that the flexible tail of PrPC wasrequired to transmit toxic signals that originate from the globular domain when this one interacts with antiPrP antibodies. Moreover, recent data showed that POM1 antibody, which targetsthe globular domain of PrPC, triggered a neurotoxic syndrome reminiscent to prion disorders in the absence of prion replication.