BIOM30002 Lecture Notes - Lecture 35: Solanezumab, Immunogen, Epitope
Document Summary
Humanise monoclonal antibody to abeta16-24 that preferentially binds soluble abeta. In ad mouse model it reversed memory deficits without affecting brain abeta load. Phase ii trials, solanezumab increased plasma and csf levels of abeta40 and abeta42, an indication that plaque load in the brain was decreased. It had no effect on behavioural outcomes (adas-cog test - gold standard cognition test) Advanced to placebo-controlled phase iii trials in mild-to-moderate ad patients. Both trials did not meet cognitive or functional primary endpoints. Secondary analysis of pooled data of the failed trials showed a modest slowing in cognitive decline in mild. Immunogen: 12 amino acid peptide human tau sequence (aa395-406), comprising phosphorylated ser396/ser404 epitope. Clinical progression: cognitively normal -> mci (mild cognitive impairment) -> dementia. Abeta and tau-mediated injury occur in cognitively normal people - very early, before they get sick. It"s too late to target a /tau-mediated injury in sick patients who already have dementia.
