RG7345 is a humanized monoclonal antibody targeting the tau phosphoepitope pS422. Tau phosphorylated at this site is considered a pathological form that has been linked to the relocalization of tau away from microtubules and toward the somato-dendritic compartment of the neuron (Buée et al., 2000).
Previously, targeting the pS422 tau epitope with active vaccination was reported to decrease levels of insoluble p422S tau and improve performance in the Y maze in the Thy-tau22 transgenic model (Troquier et al., 2012). In a triple transgenic mouse model of Alzheimer's disease, peripheral injections of anti-tau/pS422 antibodies were reported to reduce accumulation of tau pathology. The antibody was shown to enter neurons and their lysosomes, where the tau-antibody complex is proposed to be cleared (Collin et al., 2014).
In January 2015, Roche started a Phase 1, single-ascending-dose study in 48 healthy young men in the United Kingdom. The study will compare the safety and pharmacokinetic measures of six different doses to placebo, all infused intravenously. Dose escalation was adaptive.
Last Updated: 20 Nov 2015
Research Models Citations
- Buée L, Bussière T, Buée-Scherrer V, Delacourte A, Hof PR. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev. 2000 Aug;33(1):95-130. PubMed.
- Troquier L, Caillierez M, Burnouf S, Fernandez-Gomez FJ, Grosjean MJ, Zommer N, Sergeant N, Schraen-Maschke S, Blum D, Buee L. Targeting phospho-Ser422 by active Tau immunotherapy in the THY-Tau22 mouse model: a suitable therapeutic approach. Curr Alzheimer Res. 2012 Jan 23; PubMed.
- Collin L, Bohrmann B, Göpfert U, Oroszlan-Szovik K, Ozmen L, Grüninger F. Neuronal uptake of tau/pS422 antibody and reduced progression of tau pathology in a mouse model of Alzheimer's disease. Brain. 2014 Oct;137(Pt 10):2834-46. Epub 2014 Jul 31 PubMed.
No Available Further Reading